Meningococcal disease and vaccination in college students

ABSTRACT

Neisseria meningitidis is a bacterial pathogen capable of causing rapidly progressing illness from nonspecific symptoms to end-organ failure or death in a matter of hours to days. Despite the availability of meningococcal vaccines, there remains a notable disease incidence peak among individuals aged 18–19 years, with college students at increased risk for disease relative to non-college students. Between 2007 and 2017, as many as one in five colleges in the United States experienced an outbreak of meningococcal disease at their own or a nearby institution. Evidence-based strategies to promote meningococcal vaccination among students can be adapted for the college setting, but barriers exist that limit widespread implementation of these strategies by colleges. In this article, we review meningococcal disease characteristics and epidemiology among US college students, vaccination indications and coverage levels among US college students, as well as college vaccination policies and practices that can impact students’ vaccine uptake.

KEYWORDS:

• Students
• meningococcal vaccines
• college
• young adult
• review

Introduction

Neisseria meningitidis is among the most common causes of bacterial meningitis in the United States (US) with one relative peak incidence of the disease occurring among persons 18 to 19 years of age.^1,2 Students at 2- or 4-year colleges or universities (hereafter referred to collectively as colleges) are at increased risk for invasive N. meningitidis compared to non-college students.² Over 40% of the US population ages 18 to 24 years are enrolled in college.³ This figure includes 17.8 million undergraduate students and 4.3 million graduate students.⁴ Their increased risk of meningococcal disease is associated with their greater likelihood of living in college dormitories and engaging in social behaviors that facilitate the transmission of respiratory pathogens.^5–10

The first conjugate vaccine recommended to protect against N. meningitidis was licensed in the US in 2005.¹¹ The overall incidence of meningococcal disease has been declining over the last few decades, assisted by increasing vaccination prevalence. Nonetheless, sporadic outbreaks continue to occur, and college-associated outbreaks account for approximately 20% of all meningococcal outbreaks in the US.¹² Between 2007 and 2017, as many as one in five US colleges experienced an outbreak of meningococcal disease at their institution or a nearby institution according to a recent survey.¹³ In that survey, 53% of the student health representatives reported that their college required any meningococcal vaccination among their student body. Individual colleges’ vaccination mandates likely have contributed to the observed higher meningococcal vaccination coverage level among college students overall compared with non-college students.^14–17 Nonetheless, the survey suggests approximately half of all US colleges still have the opportunity to implement policies to render their students and their students’ contacts considerably less vulnerable to meningococcal disease.¹³ Past college-associated outbreaks have been estimated to cost hundreds of thousands of dollars in outbreak containment measures related to contact identification, post-exposure prophylaxis, mass vaccination, and educational campaigns.¹⁸ These costs to colleges and public health institutions do not consider the financial and psychological costs to infected individuals and society associated with meningococcal disease treatment and sequelae.¹⁹

Meningococcal vaccination is the foundation for the prevention of invasive meningococcal disease within and beyond the college setting. In this article, we review meningococcal disease characteristics and epidemiology among college students, vaccination indications and coverage levels among college students, as well as college vaccination policies and practices that can impact students’ vaccine uptake.

Meningococcal disease characteristics

Most individuals exposed to N. meningitidis do not manifest symptoms of disease but are asymptomatic bacterial carriers capable of transmitting infection to others.²⁰ Nonetheless, N. meningitidis is a fearsome pathogen that can cause rapidly progressing illness from nonspecific, “flu-like” symptoms to fulminant disease in a matter of hours or days.²⁰ The Gram-negative bacterium is transmitted by contact with large droplet respiratory secretions from ill individuals and asymptomatic carriers.²¹ Disease occurs when the pathogen invades via the nasopharynx, with patients most often presenting for clinical care with meningitis, septicemia, or both.²¹ Less commonly, patients first present with arthritis, conjunctivitis, myocarditis, pericarditis, pneumonia, or urethritis, which can progress to fulminant disease.^20,21 Among individuals with invasive disease, the mortality rate is 10–20%,^1,21–24 and among disease survivors, the rate of long-term sequelae is 10–20%.^19,21,22,24 Sequelae of invasive meningococcal disease include hearing loss, limb amputation, seizure disorder, cognitive dysfunction, and loss of independent daily functions.^19–22,24

Twelve serogroups of N. meningitidis have been described by the structure of their polysaccharide capsule.^21,25 The polysaccharide capsule is a key determinant of the bacteriums’ invasive potential. Serogroups A, B, C, W, X, and Y meningococci are responsible for most cases of invasive disease globally, but incidence by serogroup varies widely with geography.^21,26 In the US, serogroups B, C, and Y meningococci have been the most common causes of sporadic and outbreak-associated invasive disease over the past two decades when considering cases for which the serogroup has been identifiable.^1,23,26

Meningococcal vaccines

There are currently five Food and Drug Administration (FDA)-approved meningococcal vaccines available in the US (Table 1). Three of these vaccines are quadrivalent meningococcal conjugate vaccines that confer protection against serogroups A, C, W, and Y meningococci (MenACWY vaccines). These vaccines function by presenting the recipients’ immune systems with serogroups A, C, W, and Y meningococcal capsular polysaccharide structures coupled to protein carrier molecules to induce a T-cell mediated response to enhance immune response and memory.²⁶ The remaining two vaccines protect against serogroup B meningococcus (MenB vaccines). These vaccines function by presenting the recipients’ immune systems with recombinant, meningococcal subcapsular lipoproteins found in prevalent serogroup B (as well as other) meningococcal strains to induce the production of bactericidal antibodies.^21,27–29

Table 1. Meningococcal vaccines currently licensed in the United States.²¹

Vaccine product	Trade name (Manufacturer)	Antigenic agent(s)	Approved ages	Year approved
Vaccines with coverage against serogroups A, C, W and Y
MenACWY-D	Menactra (Sanofi Pasteur)	A, C, W and Y polysaccharides coupled to diphtheria toxoid protein	9 mos-55 yrs	2005
MenACWY-CRM	Menveo (GlaxoSmithKline)	A, C, W and Y polysaccharides coupled to CRM protein (mutant of diphtheria toxoid)	2 mos-55 yrs	2010
MenACWY-TT	MenQuadfi (Sanofi Pasteur)	A, C, W and Y polysaccharides coupled to tetanus toxoid protein	≥2 yrs	2020
Vaccines with coverage against serogroup B
MenB-fHbp	Trumenba (Pfizer)	fHbp lipoproteins	10–25 yrs	2014
MenB-4C	Bexsero (GlaxoSmithKline)	NHBA, NadA, fHbp, and PorA lipoproteins	10–25 yrs	2015

Abbreviations: Meningococcal groups A, C, W, and Y polysaccharide diphtheria toxoid conjugate vaccine (MenACWY-D); meningococcal groups A, C, W, and Y oligosaccharide diphtheria CRM₁₉₇ conjugate vaccine (MenACWY-CRM); meningococcal groups A, C, W, and Y polysaccharide tetanus toxoid conjugate vaccine (MenACWY-TT); meningococcal group B factor H binding protein vaccine (MenB-fHbp); four-component meningococcal group B vaccine (MenB-4C); factor H binding protein (fHbp); Neisserial Heparin Binding Antigen (NHBA); Neisserial adhesin A (NadA); Porin A (PorA).

Epidemiology of meningococcal disease on college campuses

The incidence of meningococcal disease in the US has been declining among all age groups since the 1990s;^1,16,21,30 however, there remain notable incidence peaks at three distinct life stages: infancy, late adolescence to early adulthood, and late adulthood (Figure 1).^1,30 Among individuals ages 18 to 24 years old, the average US annual incidence was 0.17 cases per 100,000 population between 2014 and 2016, with the highest incidence occurring in individuals ages 18 to 19 years old (0.29 cases per 100,000 population).² Among individuals ages 18 to 24 years old in the US, the incidence of invasive meningococcal disease for persons attending college was nearly double the incidence for persons not attending college between 2015 and 2018, suggesting that college attendance is a risk factor for invasive meningococcal disease (Table 2).^14–17 Serogroup B meningococcus was responsible for the majority of meningococcal cases among all individuals ages 18 to 24 years in the US between 2014 and 2018 (Figure 2), with a relative risk for serogroup B meningococcal disease among college students of 3.54 compared to non-college students.^2,14–17,31

Figure 1. US incidence of meningococcal disease by age group, 2006–2015.¹

Figure 2. Mean US incidence of meningococcal disease per serogroup among individuals aged 18–24 years per 100,000 population, 2015–2018.^14–17*.

Table 2. Meningococcal disease incidence in US individuals aged 18–24 years per 100,000 population by college attendance.^14–17

Year	Incidence among college students	Incidence among non-college students
2015	0.21	0.11
2016	0.29	0.15
2017	0.34	0.11
2018	0.16	0.08

While the incidence of sporadic meningococcal disease has been declining, the incidence of outbreak-associated disease has remained relatively stable over time, resulting in the proportion of cases attributable to an outbreak increasing by almost 2% from 2009 (4.5%) to 2013 (6.3%).¹² Between 2009 and 2013, one in five (22%) meningococcal outbreaks in the US occurred in college populations, with 75% of the college-related outbreaks attributable to serogroup B meningococcus.² In the 2010s, a rapid succession of serogroup B meningococcal disease outbreaks on 10 college campuses led to the development of outbreak containment planning guides and resources to aid in rapid mobilization of control and containment measures.²⁴ These outbreaks lasted from 0 to 376 days (median of 34 days) and were associated with 39 cases and two deaths (5%).²⁴

Several studies have attempted to identify risk factors for meningococcal disease among college students. Evidence from the 1990s suggests that being a first-year student living in a college dormitory, having a recent upper respiratory tract infection, consuming alcohol, patronizing bars, and smoking cigarettes are associated with increased odds of meningococcal disease among college students.^6,7 A more recent study adds participating in college fraternities and sororities and having more than one kissing partner as additional risk factors.⁸

Given that many students cross state and international borders to attend college, outbreaks of N. meningitidis initially identified on college campuses have been observed to propagate far beyond institutional borders to students’ families and community contacts.¹⁵ When outbreaks that begin on a college campus extend to the broader community, containment efforts are complicated by the additional challenges of identifying and reaching at-risk individuals for education, post-exposure chemoprophylaxis, and vaccination.²⁰

Between 2015 and 2018, 90% to 100% of US college students with a known case of meningococcal disease had previously received MenACWY vaccination, and 0% to 14% had previously received MenB vaccination.^14–17 In comparison, 38% to 75% of non-college students with a known case had previously received MenACWY vaccination, and 0% had previously received MenB vaccination.^14–17 As a consequence of the high MenACWY vaccination coverage level among college students, relatively few college-associated cases of invasive meningococcal disease were attributable to serogroup A, C, W or Y meningococcus; as a result of the lower MenACWY vaccination coverage among non-college students, a higher proportion of cases in this population was attributable to serogroup A, C, W or Y meningococcus.^24,31 Limited uptake of MenB vaccination among both college and non-college students likely explains the relatively high proportion of cases attributable to serogroup B meningococcus in both populations.^18,31

Epidemiology of N. meningitidis carriage among college students

Asymptomatic nasopharyngeal carriage of N. meningitidis is believed to contribute to the population burden of meningococcal disease.^32,33 Maiden et al. demonstrated that the prevalence of meningococcal serogroup C carriage was reduced among children who had received a conjugate meningococcal vaccine with serogroup C coverage,³⁴ and this reduction in carriage among vaccinated children was also associated with decreased disease incidence in unvaccinated children in the population.³² These findings demonstrate indirect protection of unvaccinated individuals and thereby suggest that high levels of population MenACWY vaccination may contribute to herd protection, although this has not been demonstrated with MenB vaccination.³² This is consistent with the observed effect of other conjugate vaccines that have been associated with reduced bacterial carriage among vaccine recipients and population-level herd protection.³³

In a 2015 cross-sectional survey of students at a US college that had not had experienced a recent outbreak, the prevalence of all-serogroup N. meningitidis nasopharyngeal carriage was 12.7% to 14.6%.¹⁰ In a separate study that longitudinally surveyed US students four times during the 12 months after a campus-based serogroup B meningococcus outbreak, the prevalence of all-serogroup meningococcal carriage remained relatively stable at 11% to 17% over the course of the study.⁹

Similar behavioral factors associated with invasive disease have been associated with carriage of N. meningitidis including consuming alcohol, patronizing bars, attending parties, and smoking.^5,9,10, A dose response was identified with alcohol consumption in one study with greater alcohol consumption associated with higher odds of carriage.⁵ Additional risk factors for carriage include male sex and recent upper respiratory tract infection.^9,10 Recent antibiotic use has been shown to be inversely correlated with N. meningitidis carriage.^9,10

Efficacy of meningococcal vaccines in college-age students

Knowledge of meningococcal vaccines’ clinical efficacy is relatively limited, as FDA licensure for all MenACWY and MenB vaccines has been granted based on immunogenicity and safety data due to the low incidence of meningococcal disease in the US.^21,35 For the purposes of licensure, immunogenicity studies assessed candidate vaccines’ ability to induce complement-dependent bactericidal activity in recipients.²¹ Candidate vaccines demonstrated sufficient immunogenicity by exceeding predefined serum bactericidal activity titer thresholds among a set minimum proportion of study participants.²¹

Studies have demonstrated that all three MenACWY vaccines currently licensed in the US induce overall high levels of immunity in adolescents and adults with some degree of variability in their level of protection against each of the four vaccine-included serogroups.^36–41 Additional studies have demonstrated that immunity subsequently wanes as soon as 12–22 months after primary vaccination with MenACWY-D or MenACWY-CRM, though the timing of waning antibody titers appears to vary between studies.^42,43Antibody persistence after primary vaccination with MenACWY-TT vaccine has not yet been studied. In a study of adolescents who received a MenACWY-D vaccine 4 to 6 years after primary vaccination, the booster dose induced a robust amnestic response to all four included serogroups that persisted four years later.^44,45Similar studies in adolescents and adults in the US and Puerto Rico demonstrated robust responses to booster doses of MenACWY-CRM and MenACWY-TT vaccines after primary vaccination with MenACWY-D or MenACWY-CRM at least four years earlier.^46,47

Clinical effectiveness data exist for MenACWY-D vaccine but not for MenACWY-CRM or MenACWY-TT vaccines. The overall effectiveness of MenACWY-D vaccine against meningococcal disease caused by serogroups A, C, W, and Y meningococci in adolescents is approximately 69% (95% confidence interval (CI) of 51% to 80%) up to 8 years after receipt of a single dose.²¹ While decreasing prevalence of the serogroups C, W, and Y meningococcal carrier state among adolescents and young adults has coincided with increasing population coverage with the currently licensed MenACWY vaccines, there is limited evidence demonstrating a causal link between MenACWY vaccination and reduced likelihood of becoming a meningococcal carrier.^{9,10,32,33,48}

The two MenB vaccines licensed in the US have also demonstrated high levels of immunogenicity in adolescents and adults when administered in accordance with the series recommendations, though it is important to note that available data reflect immunogenicity in a global population.^49,50 In a study conducted in Australia, Canada, and Chile, antibody titers in recipients of MenB-4C vaccine waned 4 and 7.5 years after receipt of the primary series, but a robust immune response was demonstrated when a booster dose was administered 4 and 7.5 years after the primary vaccination series.⁵¹ Similarly, in a multi-country study that included US-based sites, antibody titers in recipients of MenB-fHbp vaccine waned 12 months after completion of the primary series, but vaccines demonstrated a robust immune response when a booster dose was administered 4 years after the primary vaccine series.⁵² MenB-4C clinical effectiveness among individuals aged less than 21 years in Canada has been estimated at 79% (95% CI of -231% to 99%) four years post-vaccination, but the point estimate is difficult to interpret since the confidence interval is wide and contains the null value due to the low incidence of serogroup B meningococcal disease.⁵³ Clinical effectiveness data is not available for MenB-fHbp.

Multiple studies have failed to demonstrate an association of vaccination with either of the currently approved MenB vaccines and acquisition of carriage.^{9,28,35,48,54,55} The apparent inability of MenB vaccines to prevent acquisition of carriage suggests that MenB vaccines are unable to impact herd protection, and thus, the objective of MenB vaccination is the protection of individual vaccinees.^28,56

Safety of meningococcal vaccines in college-age students

The US-licensed serogroup A, C, W, and Y meningococcal vaccines have demonstrated acceptable safety profiles in adolescents and young adults.²¹ Among these vaccines, the most common local reactions among recipients include injection site pain, erythema, induration, and/or swelling, whereas the most common systemic reactions include headache, fatigue, malaise, and myalgia.^36–39,41 Symptoms are generally mild to moderate, and, when reported, generally resolve within three days.^36–39,41 Concurrent administration with other vaccines, such as human papillomavirus (HPV) and/or tetanus-diphtheria-pertussis vaccines, generally leads to increases in reported systemic symptoms, though immunogenicity is not significantly altered.^38,57,58 Post-licensure review of MenACWY-D vaccine considered a possible link with Guillain Barré Syndrome (GBS), but the risk of GBS post-vaccination was not significantly increased from the risk in the general population.^59,60 Similarly, with the MenACWY-CRM vaccine, post-licensure review revealed a temporal association of vaccination with Bell’s palsy, but there were several possible confounders, including medical comorbidities and concomitant vaccination of some study participants, and further investigation is required to determine causality.⁶¹ To date, no post-licensure data has become available for MenACWY-TT vaccine since its approval in 2020.

Similar to the MenACWY vaccines in adolescents and young adults, the most common local reactions in the US-licensed serogroup B meningococcal vaccines include injection site pain, erythema, and induration, and the most common systemic reactions include headache, fatigue, myalgia, and arthralgia.^49,50,62 Previous studies demonstrated non-inferiority of MenB-fHbp when concurrently administered with tetanus-diphtheria-pertussis, MenACWY-D, and HPV vaccines; however, no data exist to date regarding concurrent administration of MenB-4C with other vaccines.^63,64 Post-licensure review of MenB-4C demonstrated an association with syncopal events, but no other safety concerns for MenB-4C or MenB-fHbp.^21,65 There is a theoretical possibility of inducing Factor H autoantibodies in recipients of either MenB vaccine products since both contain fHbp, but the clinical relevance of this possibility is unknown.²¹

Recommended meningococcal vaccinations for college-aged individuals

There are an estimated 1,500 student health centers on college campuses across the US.⁶⁶ The American College Health Association (ACHA) is the largest professional organization for US-based college health practitioners with members representing over 700 colleges. The ACHA’s Vaccine-Preventable Diseases Advisory Committee annually updates its Immunization Recommendations for College Student which are designed to assist colleges in setting comprehensive vaccination policies including pre-matriculation requirements and criteria for school exclusion of unvaccinated students during vaccine-preventable disease outbreaks.⁶⁷ The ACHA vaccination guidelines are aligned with the immunization schedule recommended by the Centers for Disease Control and Prevention‘s (CDC’s) Advisory Committee on Immunization Practices (ACIP) which updates its vaccination recommendations three times per year (www.cdc.gov/vaccines/schedules/index.html).

The ACIP recommends routine administration of a first dose of MenACWY vaccine to children at ages 11 to 12 years, and a second dose at age 16 years (Table 3).²¹ Individuals of typical college age may require catch-up dosing if they did not receive MenACWY vaccination per these recommendations. Others may require booster dosing prior to starting college if they received MenACWY vaccination at a younger age than the routine recommendation. MenACWY vaccination is indicated for individuals as young as 2 months who are at increased risk for meningococcal disease for reasons including anatomic or functional asplenia including sickle cell disease, complement component deficiency including complement inhibitor medication use, infection with human immunodeficiency virus (HIV), residence in a locality experiencing an outbreak, and travel to a country where meningococcal disease is hyperendemic or epidemic. It is recommended that incoming first-year college students who will reside in a dormitory have a history of at least one dose of MenACWY vaccine received at age 16 years or older and within 5 years prior to matriculation. Incoming students who do not meet these recommendations should obtain one booster dose before starting.

Table 3. Meningococcal vaccination recommendations for US college students.^21,67*

	Serogroups A, C, W, and Y meningococcal conjugate vaccines (MenACWY-D, MenACWY-CRM, MenACWY-TT)	Serogroup B meningococcal vaccines (MenB-fHbp, MenB-4 C)
Routine vaccination	Primary: 1 dose at age 11–12 yrs Booster: 1 dose at age 16 yrs Catch-up: 1 primary dose at age 13–21 yrs with 1 booster dose at age 16–18 yrs if primary dose given at age 13–15 yrs. No booster dose if primary dose given at age 16–21 yrs	Primary: 2 doses at age 16–18 yrs based on shared decision-making. If MenB-fHbp, then 2 doses given 6 mos apart. If MenB-4 C, then 2 doses given ≥1 mo apart Booster: None unless at increased risk for meningococcal disease (see Special Indications) Catch-up: 2 doses at age 19–23 yrs based on shared decision-making. If MenB-fHbp, then 2 doses given 6 mos apart. If MenB-4 C, then 2 doses given ≥1 mo apart
Special Indications
First-year college students living in residence halls	Primary (if needed as catch-up): 1 dose ≤5 yrs before college entry and at age ≥16 yrs Booster: None if primary dose given at age ≥16 yrs and ≤5 yrs before college entry, or 1 dose if primary dose given at age <16 yrs or >5 yrs before college entry	Follow routine MenB vaccination recommendations
Persistent complement component deficiency (including use of a complement inhibitor), or anatomical or functional asplenia (including sickle cell disease)	Primary (if needed as catch-up): 2 doses ≥8 wks apart** Booster (if still high risk): 1 dose given 5 yrs after primary series, then every 5 yrs thereafter	Primary: 2 or 3 doses. If MenB-fHbp, then 3 doses given at 0, 1–2, and 6 mos. If MenB-4 C, then 2 doses given ≥1 mo apart Booster (if still high risk): 1 dose given 1 yr after primary series, then every 2–3 yrs thereafter
Human immunodeficiency virus (HIV) infection	Primary (if needed as catch-up): 2 doses given ≥8 wks apart** Booster (if still high risk): 1 dose given 5 yrs after primary series, then every 5 yrs thereafter	Follow routine MenB vaccination recommendations
Potential outbreak exposure	Primary (if needed as catch-up): 1 dose Booster (if still high risk): 1 dose if ≥5 yrs since last dose	Primary: 2 or 3 doses. If MenB-fHbp, then 3 doses given at 0, 1–2, and 6 mos. If MenB-4C, then 2 doses given ≥1 mo apart Booster: 1 dose if ≥1 yr since primary series completion
Travel to countries with hyperendemic or epidemic meningococcal disease	Primary (if needed as catch-up): 1 dose Booster (if still high risk): 1 dose given 5 yrs after primary series, then every 5 yrs thereafter	Follow routine MenB vaccination recommendations

Abbreviations: Meningococcal serogroups A, C, W, and Y polysaccharide diphtheria toxoid conjugate vaccine (MenACWY-D); meningococcal serogroups A, C, W, and Y oligosaccharide diphtheria CRM₁₉₇ conjugate vaccine (MenACWY-CRM); meningococcal serogroups A, C, W, and Y polysaccharide tetanus toxoid conjugate vaccine (MenACWY-TT); meningococcal serogroup B factor H binding protein vaccine (MenB-fHbp); four-component meningococcal group B vaccine (MenB-4C).

* Consult the Advisory Committee on Immunization Practices (ACIP) for the most recent and detailed meningococcal vaccine recommendations, including guidelines for individuals with meningococcal risk factors unlikely to apply to college students (www.cdc.gov/vaccines/hcp/acip-recs/vacc-specific/mening.html).

** If administering MenACWY-D to persons with anatomic or functional asplenia or HIV infection, then start ≥4 wks after completion of the 13-valent pneumococcal conjugate (PCV13) vaccination series.

The ACIP recommends routine administration of MenB vaccine for individuals ages 10 years and older who are at increased risk for meningococcal disease due to anatomic or functional asplenia including sickle cell disease, complement component deficiency including complement inhibitor medication use, or high potential for meningococcal exposure such as residing in a locality experiencing an outbreak (Table 3).^27,68 For individuals ages 16 through 23 years who are not at increased risk of meningococcal disease, the ACIP suggests MenB vaccination may be administered on the basis of shared clinical decision-making between patients and their healthcare practitioner. Patients who opt for vaccination should receive 2 doses of MenB vaccine administered 1 or 6 months apart depending on which product is used (MenB-4C vaccine versus MenB-fHbp vaccine, respectively). The two MenB vaccine formulations are not interchangeable, and the same product should be used for both doses.

Meningococcal vaccination precautions and contraindications

Healthcare providers should consider a 15-minute observation period for syncope after MenACWY or MenB vaccination especially for adolescent patients.²¹ If syncope occurs, healthcare providers should continue to monitor patients until it resolves. Severe allergic reaction to a previous dose of meningococcal vaccine or any component of the vaccine is a contraindication to future receipt of that vaccine. In addition, severe allergic reaction to any vaccine containing diphtheria toxoid or CRM₁₉₇ is a contraindication to receiving MenACWY-D and MenACWY-CRM vaccines. Severe allergic reaction to a tetanus toxoid-containing vaccine is a contraindication to receiving MenACWY-TT vaccine. Previous history of Guillain-Barré syndrome is a precaution for receiving MenACWY-D vaccine. Because the tip caps of prefilled MenB-4C vaccine syringes contain latex, latex sensitivity is a precaution for receiving MenB-4C vaccine. Women who are pregnant or breastfeeding should receive MenACWY vaccination if indicated but should defer MenB vaccination due to lack of sufficient safety data in pregnant and breastfeeding women. Per the CDC, healthcare providers should engage pregnant or breastfeeding women at increased risk of serogroup B meningococcal disease in shared clinical decision-making to help them decide whether or not to receive MenB vaccination.²¹

Engaging patients in shared clinical decision-making for MenB vaccination

In practice, the shared clinical decision-making recommendation for MenB vaccination means healthcare providers can decide whether or not to stock MenB vaccines, and whether or not to initiate a discussion about MenB vaccination with patients who lack disease risk factors.^69,70 In contrast to its universal recommendation for MenACWY vaccination, the ACIP does not suggest healthcare providers assume the default position of encouraging MenB vaccination for all eligible individuals. Instead, the CDC offers these points for possible discussion:

• the high severity of meningococcal disease;

• the overall low incidence of serogroup B meningococcal disease with higher incidence among college students;

• the broad efficacy of MenB vaccines against most strains of serogroup B meningococcus;

• the limited duration (approximately 1–2 years) of full protection induced by MenB vaccination;

• the evidence to date suggests that MenB vaccination has no effect on meningococcal carriage.²¹

The goal of the conversation is for healthcare providers to help patients weigh potential benefits of MenB vaccination based on personal risk factors and preferences regarding risk tolerance. According to the CDC, shared decision-making can be initiated by anyone who orders or administers vaccines including physicians, nurse practitioners, registered nurses, and pharmacists. This is relevant to college students studying outside of their hometown who may have lower access to their primary care provider than to other vaccine providers located within their college student health center or at nearby pharmacies and public health clinics.

Considering mass MenB vaccination of college students in outbreak settings

The current ACIP recommendations for MenB vaccination reflect cost-effectiveness data that suggest high cost and uncertain population-level benefit associated with implementation of a universal recommendation for vaccination of all college students. According to one study estimate, an universal MenB vaccination program for college students would require 305,000 individuals to be vaccinated to prevent 11 cases of meningococcal disease, and 2,765,000 individuals to be vaccinated to prevent 1 death.³¹ Depending on model assumptions, the incremental cost per quality-adjusted life year (QALY) gained from implementing an universal MenB vaccination program for US college students may range from $748,129 to $13.9 million.^71,72 By comparison, the current US MenACWY vaccination program is estimated to cost $212,000 per QALY gained.¹¹ Thus, while MenB vaccination provides some protective benefit to individual recipients, implementing a universal MenB vaccination recommendation for all eligible college students is not a cost-effective strategy for impacting population health.⁶⁹

Mass vaccination is a recommended containment strategy during meningococcal outbreaks due to a vaccine-included serogroup.⁷³ One modeling study varied the probability of outbreak and found that if a serogroup B meningococcus outbreak was highly probable on a college campus, mass vaccination of incoming students to that campus would be both life-saving and cost-saving.⁷² This led the study authors to suggest research into predictors of an imminent outbreak so colleges could anticipate when a mass MenB vaccination program for students would be worthwhile.

The role of state mandates in supporting college students’ meningococcal vaccination

US national data are not available for meningococcal vaccination coverage levels specifically among college students. The 2019 National Immunization Survey found that only 53.7% of US adolescents aged 17 years had received 2 or more doses and 88.9% 1 or more doses of MenACWY vaccine.⁷⁴ In the same survey, only 21.8% of individuals aged 17 years had received at least 1 dose of MenB vaccine, suggesting many adolescents reach college age inadequately vaccinated against N. meningitidis.

Multiple studies have demonstrated that state-mandated vaccination for school attendance increases population vaccination coverage levels and decreases vaccine-preventable disease incidence.^75–78 Twenty-four US states require at least a subset of college students to have received MenACWY vaccination.⁷⁹ Details of state mandates are heterogeneous with some limiting the requirement only to students who are: attending publicly funded institutions, attending 4-year institutions, younger than 21 or 22 years old, newly matriculated, attending in-person classes, residing on campus, or enrolled in a minimum number of class hours. The other 26 US states and the District of Columbia have no MenACWY vaccination mandate for college students, and no state currently requires MenB vaccination.⁸⁰

The role of colleges in supporting college students’ meningococcal vaccination

All colleges have a legal obligation to meet their state’s meningococcal vaccination policy requirements and have an ethical obligation to take steps to reduce risk of a meningococcal disease outbreak. Colleges have varying tools at their disposal to fulfill these obligations (Table 4). For instance, all colleges may request students’ meningococcal vaccination records and instate vaccination requirements with reasonable penalties for noncompliance. Colleges may also help motivate students to comply with vaccination mandates by engaging campus leaders in meningococcal education and promotion activities. Finally, colleges may help students receive MenACWY and MenB vaccinations either by administering them at their student health center or referring students to community-based vaccination providers. Several reports suggest colleges can increase vaccination coverage among students through implementation of multimodal vaccination promotion and delivery interventions.^83–85 Nonetheless, colleges typically face challenges to doing so. For instance, the mix of staff and administrators who contribute to student health on a campus depends on the college’s available resources. Some 33% to 45% of colleges do not have a full-time physician on staff within their student health center, and smaller colleges and nonresidential colleges may not have a student health center at all.^86,87 Even on campuses with a student health center, limited financial resources and personnel may preclude staff from initiating vaccination quality improvement initiatives themselves, although not necessarily from participating in initiatives organized by external groups such as professional organizations or college student health insurers.^85,88

Table 4. Strategies to increase student body meningococcal vaccination coverage levels.^18,81,82

NVAC Standard adapted for the college setting	Strategy
ASSESS the vaccination status of all students	Request vaccination records of all students prior to matriculation, and then annually, as well as at every visit to the student health center Routinely consult the local or state immunization information system to check for student vaccination records
Strongly RECOMMEND vaccination to students	Create a policy requiring student proof of vaccination with defined timetable and reasonable consequences for noncompliance Send new students vaccine educational materials in their prematriculation packets Enlist college leaders (including student government representatives, residential counselors, student newspaper journalists and athletic coaches) in vaccine promotion efforts Educate all student health center staff on providing a strong vaccination recommendation Outreach to students when they are due or overdue for vaccination
ADMINISTER vaccinations if able or REFER students to an outside vaccination provider if not	Allow students to walk into the health center without an appointment to get vaccinated Offer vaccination services on evenings and weekends If indicated, offer vaccination at every health center visit, regardless of the presenting complaint Coordinate vaccination events in high-traffic locations across campus staffed by health center personnel or community-based vaccinators
DOCUMENT vaccinations received by students	Document students’ vaccination status in a single, electronic immunization record Submit students’ vaccinations to the local or state immunization information system

In addition to promoting routine meningococcal vaccination among students, college health administrators should consider their level of preparedness for mass meningococcal vaccination in the event of a campus outbreak. According to the CDC, considerations for launching a mass vaccination campaign in the event of a meningococcal outbreak (not specific to the college setting) include the number of index cases, population size, ability to identify potential vaccinees, likelihood of ongoing transmission, feasibility, and likely lag time between identification of index cases and vaccination in earnest.⁷³ In a survey of ACHA members, fewer than half of the respondents reported that their college had a plan that included administration of MenACWY or MenB vaccines to students in the event of a campus meningococcal outbreak.⁸⁹ Lessons learned from the Coronavirus Disease 2019 (COVID-19) pandemic, as well as college-specific guidance from the CDC and ACHA on pandemic preparedness, should be used by college health authorities and public health officials to plan for a campus outbreak of meningococcus with protocols that include the potential administration of meningococcal vaccines to students.^90,91

Financial obstacles to high meningococcal vaccine coverage levels among college students

The limited investment by some colleges in student health has been described in lay publications and is not necessarily inappropriate, especially at smaller institutions, given their primary mission of education. Nonetheless, the situation presents a barrier to some colleges’ ability to intervene to achieve a high meningococcal vaccination coverage level among their students. A 2020 examination by the Washington Post of 1500 4-year, residential colleges with at least 500 students enrolled revealed that 16.7% did not have a student health center, although some without a campus health center did offer students medical services via telehealth or partnership with off-campus healthcare providers.⁸⁷ According to the Washington Post, the average amount 200 colleges with a health center spent per student on health center services in 2017 was only $185. With such a limited budget, vaccine promotion and administration may pose a strain on the resources of some student health centers. The net effect of the COVID-19 pandemic on colleges’ future investment in student health is unclear. In an ACHA survey of its membership from August 2020, 43.5% of 207 respondents anticipated a reduction to their student health center budget in 2021.⁹²

In 2021, the manufacturer contract price per dose in the US ranged from approximately $135 to $140 for MenACWY vaccine and from $157 to $192 for MenB vaccine.⁹³ Thus, even at colleges with student health centers that have the capacity to stock and administer vaccines, cost may restrict access to meningococcal vaccinations. In a recent survey of 147 college health administrators and clinicians across the US, the most frequently cited barriers to being able to offer students MenB vaccination services were financial in nature.⁸¹ Over half of respondents felt that the limited ability of their health center to pay up front to stock the vaccine and of students to pay the out-of-pocket costs to receive the vaccine were major barriers to having a MenB vaccination program at their college.⁸¹ This is in contrast to findings from a separate survey of US community-based healthcare providers in which financial burden was reportedly the most impactful parameter in less than 10% of their decisions not to prescribe MenACWY or MenB vaccination for their eligible patients.⁹⁴

In terms of meningococcal vaccination reimbursement, most college student health centers do not have the infrastructure required to support broad health insurance billing.⁹⁵ As a result, many derive their operational budgets from an annual health fee assessed to students which covers basic services with additional services rendered at additional charge. Student health centers reliant on the health fee model may be unable to include meningococcal vaccinations as fully covered services, and students may be unwilling or unable to pay more than a nominal cost to be vaccinated. Low student body demand for meningococcal vaccination may induce low levels of enthusiasm among health center administrators for purchasing vaccine supply since there is risk that stock will expire before it can be administered.

Some college student health centers that do not operate under the health fee model instead accept a limited number of insurance plans designed exclusively for students.⁹⁵ These student health insurance plans (SHIPs) may be funded directly by the school or through an unaffiliated insurer. The ACHA standards call on these SHIPs to include all ACIP-recommended immunizations, including MenACWY and MenB vaccinations, as fully covered services.⁹⁶ Even so, the ACHA also suggests that short-term, limited duration insurance (STLDI) plans for students “could be appropriate in limited circumstances.”⁹⁷ Such plans typically do not cover vaccinations.

Individuals covered by a school-funded SHIP may be limited in the healthcare they can receive outside of the college health center setting or may lose coverage over the summer if they do not meet minimum course enrollment criteria or transfer to a different college.⁹⁸ Passage of the Affordable Care Act (ACA) by the US Congress in 2010 has permitted a greater number of students to maintain their childhood health plans through their college years since the law specifies that dependents may remain on their parents’ or guardians’ insurance plan until age 26 years.⁹⁹ Additionally, the ACA requires health plans (with a few exceptions such as STLDI plans) to cover all ACIP-recommended vaccinations. Nonetheless, students that attend college outside of the state in which they are insured under a parent’s plan may have difficulty finding a vaccination provider in their college town that participates in their out-of-state health plan.

Meningococcal vaccination delivery and promotion best practices for colleges

The US National Vaccine Action Coalition (NVAC) has published Standards for Adult Immunization Practice designed to enhance vaccine uptake.⁸² These standards call on healthcare providers to engage in the following practices, regardless of whether or not they administer vaccinations:

• ASSESS the immunization status of all patients at every healthcare visit;

• Strongly RECOMMEND indicated vaccinations to patients;

• ADMINISTER all indicated vaccinations if able, or REFER patients to an outside vaccinator if not;

• DOCUMENT vaccinations received by patients.

In addition to NVAC standards, immunization experts have compiled evidence-based strategies likely to enhance vaccination coverage levels on college campuses.^18,81 These strategies are consistent with NVAC standards (Table 4). To the best of their ability, colleges should endeavor to implement these standards and strategies in their meningococcal vaccination practices and policies, regardless of whether they can administer meningococcal vaccinations to students.

Assessing college students’ meningococcal vaccination status

Colleges should assess their students’ meningococcal vaccination status at a minimum on an annual basis, prior to the start of the academic year. This is a formidable task given the influx of new students admitted each year. In one survey involving 147 colleges, 77.3% and 46.9% of the respondents reported requesting records of all students for MenACWY and MenB vaccination, respectively.⁸¹ At colleges with limited or no healthcare staff and where verification of students’ MenACWY vaccination is state mandated, data collection may be completed by nonclinical administrators with little to no experience interpreting the validity of vaccinations. Besides collection of student-submitted records, vaccination assessments should also include searches of the local or state immunization information system for additional student vaccination records.¹⁸ Searches of the local or state immunization information system may be more fruitful for colleges with a high percentage of in-state students.

At colleges with student health centers, students’ vaccination status should be assessed at each healthcare encounter, as well. Physical vaccination records obtained from students upon matriculation should be entered into the student health center’s record system to permit healthcare providers to easily determine whether students presenting for care should opportunistically be offered or referred for meningococcal vaccinations that day.

Giving a strong MenACWY vaccination recommendation to college students

In the college setting, providing a strong vaccination recommendation includes having a robust school policy supportive of vaccination. While states rarely require students to have received all ACIP-recommended vaccinations, 45% to 65.3% of colleges require students to have received at least one additional vaccination beyond the minimum mandated by their state.^100,101 Surveys of colleges conducted from 2014 to 2018 reveal MenACWY vaccination to be among the top three and MenB vaccination among the bottom two most commonly required vaccinations.^81,100,101 In these surveys, 51.9% to 73.7% of colleges reported requiring MenACWY vaccination, and 0.93% to 10.5% reported requiring MenB vaccination.^{81,89,100,101} Various college characteristics have been associated with having a student MenACWY vaccination requirement including being located in a state with a vaccination mandate, having a smaller study body, and being privately funded.^89,101

Most colleges with a meningococcal vaccination mandate require students to submit proof of vaccination, such as a physician-signed vaccination record or a written request for an exemption from the vaccination requirement.⁸⁹ The conditions under which an exemption is granted vary. In one survey, almost a quarter of colleges (23.7%) required students who desired an exemption to receive meningococcal vaccination counseling by a healthcare provider first.⁸⁹ In a survey conducted from 2014 to 2015, 98% of the colleges permitted students to be exempted from vaccination requirements in general based on their religious beliefs and 54% based on their philosophical beliefs.¹⁰¹

After a grace period, colleges may apply various penalties to students who are not in compliance with their vaccination policy including preventing course registration, imposing fees, barring access to campus housing, restricting class attendance, preventing participation in organized sports, and excluding them during an outbreak.^100–102 Preventing course registration is the most common consequence applied, with 56% to 89% of colleges choosing this enforcement strategy.^100–102

For colleges that have a student health center, healthcare providers should convey the importance of MenACWY vaccination to all students and engage them a discussion about MenB vaccination. In a qualitative study involving 33 college students, participants expressed low knowledge about vaccines in general, and low perceived risk for vaccine-preventable disease outbreaks.¹⁰³ Participants also expressed a high degree of trust in the advice of medical professionals with respect to vaccine decision-making. This suggests the value of student healthcare providers taking the time to educate students about meningococcal disease and the benefits of vaccination since students may have little preexisting knowledge.

Administering meningococcal vaccination or referring students for off-campus vaccination

Student health center providers should broach meningococcal vaccination with all eligible students regardless of their presenting complaint since only 9% of student health center visits are made for the primary purpose of vaccination.⁶⁶ After discussion and obtaining consent, health center providers should either administer MenACWY and/or MenB vaccinations on site or refer students to community-based vaccine providers.

Among colleges with a student health center, approximately half stock MenACWY vaccine, and 25% to 37% stock MenB vaccine.^81,89 Surveys suggest health center providers may not use every opportunity to offer meningococcal vaccinations to students even when the vaccines are available; in one survey, approximately 23% of respondents did not order and administer MenACWY vaccine to students even though it was stocked, and in another, slightly under half did not routinely do so at each healthcare encounter.^81,89 In addition, not all student health center providers give students information about how to receive meningococcal vaccination in the community; in surveys, 59.9% of student health center providers reported referring students to community-based providers for MenACWY vaccine, and 55.1% to 62.1% for MenB vaccine.^81,89

Students value convenience in receiving vaccinations.¹⁰⁴ As such, colleges should maximize the accessibility of their vaccination services. One survey suggests a minority of colleges ever hold outreach events to administer MenACWY (21.5%) or MenB vaccine (8.4%) to students at high-traffic locations across campus.⁸¹ Greater percentages of colleges permit their students to walk into their student health center to receive a MenACWY or MenB vaccination without an appointment (64.9% and 57.7%, respectively).⁸¹

Documenting vaccinations administered to students

Meningococcal vaccinations administered in the student health center or by community-based vaccine providers should be documented in the student’s health center record with a copy given to the student. Ideally, the health center’s electronic medical record system interfaces with the local or state immunization information system for bidirectional data exchange. The electronic health record systems used most frequently by college health centers are designed specifically for the college health setting. The ease with which health center providers can enter and access vaccination data, as well as customize vaccination data entry pages, varies across systems. Smaller student health centers may lack sufficient technological support to optimize their vaccination entry pages.⁸⁶ In a survey, 56.7% of respondents reported documenting their students’ MenACWY vaccination status, and 42.5% their MenB vaccination status at each health center encounter.⁸¹

Conclusions and prospects

Colleges are uniquely positioned to promote meningococcal vaccine uptake among young adults, a population at higher risk for meningococcal disease than other age groups. Colleges with or without student health centers have many options for adopting meningococcal vaccine-friendly policies that are consistent with NVAC recommendations. Nonetheless, their engagement in promoting meningococcal vaccination to students is often limited by motivational, logistical, and financial barriers. Motivational barriers could be reduced if more states were to pass legislation requiring meningococcal vaccination of college students, especially if the mandates were to restrict or prohibit religious and philosophical exemptions. Logistical barriers could be reduced if the federal government were to deploy a national vaccination registry to facilitate colleges’ access to students’ vaccination records regardless of students’ home state. Additional logistical barriers could be reduced if health insurers were to offer college student health centers the ability to participate in organized learning collaboratives to assist them with implementing meningococcal vaccine delivery best practices. Finally, financial barriers could be reduced if national legislation were passed requiring commercial insurance plans and SHIPs to cover all vaccination costs for college students regardless of whether care was delivered by an in-network healthcare provider.

Abbreviations

Table

Advisory Committee on Immunization Practices	ACIP
Affordable Care Act	ACA
American College Health Association	ACHA
Centers for Disease Control and Prevention	CDC
Coronavirus Disease 2019	COVID-19
Food and Drug Administration	FDA
Four-component meningococcal group B vaccine	MenB-4C
Factor H binding protein	fHbp
Guillain Barré Syndrome	GBS
Human immunodeficiency virus	HIV
Human papilloma virus	HPV
Meningococcal groups A, C, W, and Y polysaccharide diphtheria toxoid conjugate vaccine	MenACWY-D
Meningococcal groups A, C, W, and Y oligosaccharide diphtheria CRM197 conjugate vaccine	MenACWY-CRM
Meningococcal groups A, C, W, and Y polysaccharide tetanus toxoid conjugate vaccine	MenACWY-TT
Meningococcal group B factor H binding protein vaccine	MenB-fHbp
National Vaccine Advisory Committee	NVAC
Neisserial Heparin Binding Antigen	NHBA
Neisserial adhesin A	NadA
Porin A	PorA
Quality adjusted life year	QALY
Short-term, limited duration insurance	STLDI
Student health insurance plan	SHIP
United States	US

Disclosure of potential conflicts of interest

In accordance with Taylor & Francis policy and our ethical obligation as researchers, we are reporting the following interests: Sarah Schaffer DeRoo is a consultant to Pfizer, Inc. Linda Y. Fu has received research support from Pfizer, Inc., which has also provided salary support for Rachel Torres.

Disclosure statement

No potential conflict of interest was reported by the author(s).