Rotavirus vaccines

Figures & data

Figure 1. 10 countries with the greatest number of rotavirus deaths in 2008. Adapted from: Tate et al. 2008 estimate of worldwide rotavirus-associated mortality in children younger than 5 y before the introduction of universal rotavirus vaccination programmes: a systematic review and meta-analysis. Lancet Infect Dis 2012; 12(2):136–141.

Table 1. Currently licensed and globally recommended rotavirus vaccines

Characteristic	Rotavirus vaccine
Trade name	Rotarix^®	RotaTeq^®
Manufacturer	GlaxoSmithKline	Merck and Co., Inc.
Country of manufacture	Belgium	USA
Composition	Live-attenuated G1P1A[8] human rotavirus strain	Live human-bovine reassortant rotavirus strains: G1P7[5], G2P7[5], G3P7[5], G4P7[5], G6P1A[8]
Pharmaceutical form	Liquid, lyophilized + diluent	Liquid
Presentation	1 dose plastic tube or 1 dose applicator or 1 dose vial	1 dose tube
Route of administration	Oral	Oral
Recommended schedule of administration	Minimum age of 1st dose: 6 wk 2 doses at least 4 wk apart Previous WHO recommendations for upper age limits of 15 wk for the first dose and 32 wk for second dose have been removed	Minimum age of 1st dose: 6 wk 3 doses at least 4 wk apart Previous recommendations for upper age limits of 15 wk for first dose and 32 wk for third dose have been removed
Contraindications per manufacturer	Hypersensitivity to the active substance or to any of the excipients; hypersensitivity after previous administration of rotavirus vaccines; history of intussusception; history of uncorrected congenital malformation of the gastrointestinal tract that would predispose for intussusception; history of severe combined immunodeficiency disease (SCID)	A demonstrated history of hypersensitivity to the vaccine or any component of the vaccine; history of severe combined immunodeficiency disease (SCID); history of intussusception
Volume per dose	1.5 mL (tube and applicator) 1 mL (lyophilized + diluent)	2 mL
Cost per dose	GAVI-eligible: $2.43 (2014 UNICEF pricing) Non-GAVI: variable	GAVI-eligible: $3.50–5.00 (2014 UNICEF pricing) Non-GAVI: variable
Date of WHO prequalification	Mar 2009 (tube and applicator) Jan 2007 (vial)	Oct 2008
Licensure status	Licensed in >100 countries	Licensed in >100 countries
Full series efficacy against severe rotavirus gastroenteritis (95% confidence interval)	3-y follow-up: 97% (88–100) (Hong Kong/Singapore/Taiwan) 2-y follow-up: 81% (71–87) (Latin America) 90% (85–94) (Europe) 72% (54–84) (China) 92% (62–99) (Japan) 1-y follow-up: 49% (11–72) (Malawi) 72% (40–88) (South Africa)	3-y follow-up: 94% (89–97) (Finland) 1-y follow-up: 98% (88–100) (US/Finland) 51% (13–73) (Bangladesh/Vietnam) 64% (40–79) (Kenya/Ghana/Mali) Up to 1-y follow-up: 100% (55–100) (Japan)

Table 2. Rotavirus vaccines that are regionally used, recently licensed, or in development

Name	Composition	Route of administration	Organization/Company	Stage of development
Lanzhou Lamb Rotavirus (LLR)	Live attenuated lamb rotavirus strain, G10P[12]	Oral	Lanzhou Institute of Biological Products, China	Licensed for use in China
Rotavin-M1	Live attenuated human rotavirus strain, G1P[8]	Oral	POLYVAC, Vietnam	Licensed for use in Vietnam
ROTAVAC	Live attenuated neonatal rotavirus strain, G9P[11] (aka 116E)	Oral	Bharat Biotech, India	Recently licensed for use in India; pursuing WHO pre-qualification
LLR reassortants	Live attenuated lamb-human reassortant rotavirus strains, G2, G3, G4	Oral	Lanzhou Institute of Biological Products, China	Phase III
RotaShield	Live attenuated rhesus-human reassortant rotavirus strains, tetravalent	Oral	International Medica Foundation, USA	Phase II complete, Phase III pending
RV3	Live attenuated neonatal rotavirus strain, G3P[6]	Oral	Biofarma, Indonesia	Phase II
UK reassortants	Live attenuated bovine-human reassortant strains, tetravalent to hexavalent	Oral	National Institutes of Health, USA; Instituto Butantan, Brazil; Serum Institute of India, India; Shantha Biotech, India; /Minghai Biotechnology Co., China; Wuhan Institute of Biological Products, China	Phase I and II, Research
NF-R7	Live attenuated lamb-human reassortant strain, G4	Oral	Shenzhen Kangtai Biological Products Company, China	Phase I
Subunit	Truncated VP8 of P4, P6, P8	Intramuscular	National Institutes of Health and PATH, USA	Phase I
IRV	Inactivated G1P[8], G2P[4]	Intramuscular or intradermal	US CDC; multiple (China, Europe, India)	Pre-clinical
Subunit	Virus-like particles: VP 2/6/7 and VP 2/4/6/7	To be determined	Baylor College of Medicine, USA	Research
Subunit	Truncated VP8 in norovirus P particles	To be determined	Cincinnati Children’s Hospital Medical Center, USA	Research
Subunit	VP6 combined with norovirus G1 and GII VLPs	To be determined	University of Tampere School of Medicine, Finland	Research

Figure 2. National rotavirus vaccine introductions, by geographic region—56 countries*

Table 3. Summary of rotavirus vaccine impact studies among children <5 y – disease trends^a

Location	Vaccine	% Reduction	References
Reduction in diarrheal death rates
Brazil      • Nationwide      • Nationwide	Rotarix Rotarix	22% 33–39%	27 28
Mexico, Nationwide	Rotarix	46%	29
Panama, Nationwide	Rotarix	32–50%	26
Reduction in diarrhea hospitalizations
Australia      • National      • Queensland      • South Australia	Rotarix, RotaTeq RotaTeq RotaTeq	38% 20–40% 48% (0 to <6 y)	36 37 32
Belgium, Nationwide	Rotarix, RotaTeq	33% (0 to 2 y)	42
Brazil      • Nationwide      • Nationwide      • Sao Paolo      • Sergipe	Rotarix Rotarix Rotarix Rotarix	26–48% (0 to 1 y) 17% 29% 44–55%	39 27 43 38
El Salvador, Nationwide	Rotarix	28–37% (includes outpatient)	44
Mexico, Nationwide	Rotarix	40% (during rotavirus season)	41
Panama, Bocas del Toro, Chiriquí, Los Santos, San Miguelito, Metropolitan Region	Rotarix	37%	40
USA      • Nationwide      • Nationwide      • 3 regions (Northeast, Midwest, South)      • Privately insured children, 13 states^b      • New Orleans, LA      • New York, NY	RotaTeq RotaTeq RotaTeq RotaTeq RotaTeq RotaTeq	45% (during rotavirus season) 29–50% 30–45% 25–33% 50% 40% (0 to <2 y)	35 45 34 33 30 31
South Africa, Gauteng and Mpmalange provinces	Rotarix	32–33%	51
Reduction in rotavirus hospitalizations
Australia      • National      • New South Wales, Queensland, Victoria      • Queensland      • Queensland      • South Australia	Rotarix, RotaTeq Rotarix, RotaTeq RotaTeq RotaTeq RotaTeq	71% 87% 53–57% 50% 83% (0–71 mo)	36 47 51 37 32
Austria      • Nationwide      • Nationwide      • Nationwide      • Tyrol	Rotarix, RotaTeq Rotarix, RotaTeq Rotarix, RotaTeq Rotarix, RotaTeq	70% (0 to 1 y) 76–79% (0 to 2 y) 73–74% 62–88%	55 54 53 59
Belgium      • Nationwide      • Leuven	Rotarix, RotaTeq Rotarix, RotaTeq	58–77% 49–66%	42 58
Finland, Tampere	Rotarix, RotaTeq	91% (<2 y; incl. ER visits)	50
Brazil, Sao Paolo	Rotarix	59%	43
El Salvador, San Salvador, Santa Ana, San Miguel, La Libertad, La Paz	Rotarix	69–81%	44
USA      • Nationwide      • Nationwide      • 3 regions (Northeast, Midwest, South)      • Privately insured children, 13 states^b      • Chicago      • Cincinnati, OH, Nashville, TN, Rochester, NY      • Jacksonville, FL      • New Orleans, LA      • New York, NY      • US military dependents	RotaTeq RotaTeq RotaTeq RotaTeq RotaTeq RotaTeq RotaTeq RotaTeq RotaTeq RotaTeq	67–69% 66–83% 69–81% 60–75% 62% (during viral season) 55–89% (0 to 35 mo) 72% 67% (includes ED visits) 85% (0 to <2 y) 62%	57 45 34 33 46 56 48 30 31 49
South Africa, Gauteng and Mpmalange provinces	Rotarix	40–44%	52

^a Estimated rotavirus vaccination coverage ranges of 37–94% mostly among children 0–1 y or 0–2 y, if reported. ^bAlaska, Idaho, Massachusetts, Maine, North Dakota, New Hampshire, New Mexico, Oregon, Rhode Island, Vermont, Washington, Wisconsin, Wyoming.

Table 4. Summary of rotavirus vaccine impact studies – indirect benefits for unvaccinated individuals^a

Location	Vaccine	Age range	% Reduction	References
Reduction in diarrhea hospitalizations
Australia      • Queensland      • South Australia	RotaTeq RotaTeq	2 to 4 y 2 to <6 y	30–40% 42–49%	37 32
USA      • Nationwide      • Nationwide      • Nationwide      • Nationwide      • Nationwide      • New Orleans, LA      • New York, NY      • New York, NY      • New York, NY	RotaTeq RotaTeq RotaTeq RotaTeq Rotarix, RotaTeq RotaTeq RotaTeq RotaTeq RotaTeq	2 to <5 y 2 to <5 y 5 to 24 y 5 to 44 y 2 to <5 y 2 to <3 y 3 to <5 y 5 to 18 y	35–41% 43–45% 17–48% (during rotavirus season) 8–29% 6–30% 51% 31–36% 33–37% 9–12%	34 35 45 62 61 30 31 31 31
Reduction in rotavirus hospitalizations
Australia      • Queensland      • South Australia	RotaTeq RotaTeq	2 to 19 y 2 to <6 y	30–70% 50–83%	37 32
Austria      • Nationwide      • Tyrol	Rotarix, RotaTeq Rotarix, RotaTeq	2 to 5 y 2 to 18 y	35% 62–89%	54 59
Belgium, Nationwide	Rotarix, RotaTeq	2 to 5 y	20–64%	42
Finland, Tampere	RotaTeq	2 to <16 y	72%	50
Brazil, Sao Paolo	Rotarix	2 to <5 y	24%	43
El Salvador, Nationwide	Rotarix	2 to <5 y	41–81%	44
USA      • Nationwide      • Nationwide      • Nationwide      • Nationwide      • Chicago, IL      • Cincinnati, OH, Nashville, TN, Rochester, NY      • New York, NY      • New York, NY      • New York, NY      • US military dependents	RotaTeq RotaTeq RotaTeq Rotarix, RotaTeq RotaTeq RotaTeq RotaTeq RotaTeq RotaTeq RotaTeq	2 to <5 y 2 to <5 y 5 to 24 y 5 to 44 y ≥18 y 2 to <3 y 2 to <3 y 3 to <5 y 5 to 18 y 0 to 4 y	69–78% 41–80% 65–71% 43–70% 48% 92% 70–76% 79–88% 70% 57% (unvaccinated individuals)	34 45 62 61 63 56 31 31 31 49

^a Estimated rotavirus vaccination coverage ranges of 37–94% mostly among children 0–1 y or 0–2 y, if reported.

Table 5. Vaccine effectiveness (VE) against rotavirus hospitalizations

Location	Vaccine type	Vaccine effectiveness	Predominant strain	References
Australia      • Queensland      • Central Australia      • Central Australia	RotaTeq Rotarix Rotarix	94% 84% 51%	G9P[8] G2P[4]	37 80 79
Taiwan, Linkou, Changhua, Kaohsiung	Rotarix, RotaTeq	92%, 97%	G1P[8]	69
Austria, Nationwide	Rotarix, RotaTeq	79–96%	G1P[8], G2P[4]	53
Belgium, Nationwide	Rotarix	90%	G2P[4]	67
France, Nortwest Britanny	RotaTeq	98%		74
Germany, Mecklenberg-Western Pomerania	Rotarix, RotaTeq	80%	G1P[8], G9P[8]	64
Northern Israel	Rotarix, RotaTeq	89%		77
Spain      • Nationwide      • Navarre	Rotarix, RotaTeq Rotarix, RotaTeq	97%, 95% 83%	G9	76 68
Bolivia	Rotarix	69–77%	G9P[8], G2P[4], G3P[8], G9P[6]	89
Brazil      • Northeast Brazil      • Recife      • Belem	Rotarix Rotarix Rotarix	89–95% 80–81% 40–76%	G2P[4] G2P[4] G2P[4]	38 70 75
El Salvador, Nationwide	Rotarix	76%	G1P[8]	85
Mexico, Chiapas	Rotarix	94%	G9P[4]	83
Nicaragua, Nationwide      • Nationwide      • Managua, Jinotepe, Masaya, Matagalpa      • Western Region      • Western Region	RotaTeq RotaTeq RotaTeq RotaTeq	43–49% 45–70% 64–87% (includes ED visits) 72–92% (includes ED visits)	G2P[4] G1P[8], G2P[4]	87 88 86 84
USA      • Nationwide      • Houston, TX      • Houston, TX      • Cincinnati, OH, Nashville, TN, Rochester, NY      • Cincinnati, OH, Nashville, TN, Rochester, NY      • CA,MO,NY,OH,TN,TX,WA      • New Haven, CT      • CT, GA      • CT, GA, MN	RotaTeq RotaTeq RotaTeq RotaTeq RotaTeq RotaTeq RotaTeq Rotarix, RotaTeq RotaTeq	100% 100% 83–86% (includes ED visits) 95% 92% (includes ED visits) 86% 94–97% 94–98%, 97% 90–92%	G3P[8] G3P[8] G1-G3, G9, G12 G1P[8] G1P[8], G2P[4], G3P[8], G12P[8] G1-G4, G9 G1P[8], G2P[4]	82 65 66 81 73 78 72 71 60

Table 6. Risk of intussusception and benefits of rotavirus vaccination in Mexico, Brazil, Australia, and the US^a

Country	Diarrhea hospitalizations (deaths) prevented by vaccination	Intussusception cases (deaths) potentially caused by vaccination	Reference
Mexico	11 600 (663)	41 (2)	94
Brazil	69 600 (640)	55 (3)	94
Australia	7000 (0)	6 (0)	102
US	53 444 (14)	45–213 (0.1–0.5)	103

^a Data are for one fully vaccinated birth cohort followed to age 5 y.

Table 7. Key issues and potential barriers and related questions in the decision to introduce rotavirus vaccine

Key issues	Potential barriers/concerns	Related questions	Potential solutions
Policy-related
Rotavirus/diarrheal disease as a public health priority	Competing priorities (e.g., other new vaccine introductions, other health interventions on the public health agenda)	Do policy makers have sufficient information to appropriately prioritize rotavirus vaccine?	Ensure that existing disease burden and vaccine information and impact data available to policy makers
Evidence of disease burden	• Lack of local disease burden data • Lack of regional disease burden data	• Is the local rotavirus disease burden similar to other countries? • What is the rotavirus disease burden in other countries in the region?	• Establish sentinel rotavirus surveillance • Communicate with regional partners to share available disease burden data
Vaccine efficacy, quality and safety	• Lack of local efficacy/effectiveness data • Concerns about intussusception	• Will the current vaccines be able to provide protection against the local rotavirus strains? • Why is vaccine efficacy worse in lower income countries? • Will vaccine use be associated with an increase in intussusception cases in my country?	• Provide existing rotavirus strain-specific effectiveness data • Investigate strategies to improve vaccine uptake • Develop vaccines with improved efficacy (e.g., parenteral vaccines) • Establish baseline intussusception rate and/or post-introduction intussusception surveillance if possible
Existing interventions to prevent rotavirus	Lack of awareness regarding the role of rotavirus vaccine as the main means of prevention	Won’t improve access to clean water and sanitation prevent rotavirus disease?	Improve communication about the role of rotavirus vaccines as the current mainstay for rotavirus prevention
Economic and financial issues (e.g., cost-effectiveness, fiscal impact, financial sustainability)	• High cost of existing rotavirus vaccines • Lack of cost-related analyses	• Will rotavirus vaccines ever be sold at a lower price? • What is the potential cost-effectiveness of a rotavirus vaccination program? • What is the potential fiscal impact of rotavirus vaccine introduction on the immunization program?	• Ensure affordable vaccine prices • Conduct cost-effectiveness and fiscal impact evaluations in countries that have not introduced vaccine
Program-related
Vaccine presentation	Vaccine packaging will take up too much cold chain space	Is there sufficient cold chain capacity for rotavirus vaccines? If not, how can we increase capacity?	Support cold chain assessments (i.e., Effective Vaccine Management) and expansion as needed
Vaccine supply availability	Available vaccine supply insufficient to accommodate national introduction	Will there be enough vaccine supply for the country’s target population?	Work with vaccine manufacturers to ensure sufficient global vaccine supply
Strength of the existing immunization program	Current routine immunization program not ready to introduce a new vaccine (e.g., insufficient capacity to accommodate new vaccine, insufficient resources - funding and/or staff - to conduct training sessions and social mobilization)	How will we be able to acquire the resources and technical support required to introduce rotavirus vaccine?	Provide technical support for vaccine introduction planning and implementation, including potential means for acquiring necessary funding