Progress towards RSV Vaccine
A respiratory syncytial virus vaccine candidate RSV F (Novavax) was successful in a placebo-controlled Phase 2 trial involving 1600 older U.S. adults. It prevented 64% of severe RSV infections, 44% of all symptomatic RSV cases, and 46% of lower respiratory tract symptoms. RSV F, along with another candidate from MedImmune, has received FDA fast-track designation. It is in a second Phase 2 study involving pregnant women to assess safety and immunogenicity in newborns.
Another RSV vaccine to enter clinical trials is MVA-BN RSV (Bavarian Nordic). A placebo-controlled Phase 1 will involve 63 U.S. adults divided into three groups in a dose-escalating manner.
A third candidate, a recombinant VLP-based vaccine, protected mice from disease when challenged one year after vaccination. According to results published in International Journal of Nanomedicine,1 the animals showed no signs of severe pulmonary disease, lower levels of inflammation markers and higher levels of antibodies compared to a control group.
RSV causes serious respiratory infections in infants and older adults and is a leading cause of bronchiolitis and lung inflammation in U.S. children. There is no available RSV vaccine.
1. Lee YT, Ko EJ, Hwang HS, Lee JS, Kim KH, Kwon YM, Kang SM. Respiratory syncytial virus-like nanoparticle vaccination induces long-term protection without pulmonary disease by modulating cytokines and T-cells partially through alveolar macrophages. Int J Nanomedicine 2015; 10:4491-505.
Routine 2-dose Vaccination led to substantial decrease in Chickenpox
Chickenpox-related hospitalizations in the U.S. dropped by 93% and outpatient visits decreased by 84% following the recommendation in 2006 for a 2-dose varicella vaccination schedule, according to a CDC study published in Journal of Pediatric Infectious Diseases Society.1
The authors compared national health insurance claims record of 1994-5 (before vaccine was available) and 2006-12. They found that the 2-dose vaccination correlated with fewer hospitalizations than both the pre-vaccination period and the 1-dose schedule recommended in 1996-2006. Notably, age groups not targeted for vaccination were also protected due to herd immunity.
Chickenpox is caused by the highly contagious varicella-zoster virus. Infected individuals develop skin rash, fever and headaches, and sometimes pneumonia or meningitis.
1. Leung J, Harpaz R. Impact of the Maturing Varicella Vaccination Program on Varicella and Related Outcomes in the United States: 1994–2012. J Ped Infect Dis 2015; doi: 10.1093/jpids/piv044
rVSV-ZEBOV 100% efficacious against Ebola
Interim results from a Phase 3 clinical trial showed that an Ebola vaccine candidate rVSV-ZEBOV (Merck) provides rapid and complete protection.1 The study is ongoing, with 4,000 subjects having received an injection immediately after exposure to the virus. The vaccine group reported no cases of Ebola after 10 days, compared to 16 cases in the placebo group.
The ‘ring study’ takes place in Guinea and recruits at-risk individuals around Ebola cases, aiming to create a ring of protection. The target number of subjects is 7,000, but the receding epidemic makes it difficult for researchers to find additional participants for clinical trials.
1. Henao-Restrepo AM, Longini IM, Egger M, Dean NE, Edmunds WJ, Camacho A, Carroll MW, Doumbia M, Draguez B, Duraffour S, Enwere G, Grais R, Gunther S, Hossmann S, Kondé MK, Kone S, Kuisma E, Levine MM, Mandal S, Norheim G, Riveros X, Soumah A, Trelle S, Vicari AS, Watson CH, Kéïta S, Kieny MP, Røttingen JA. Efficacy and effectiveness of an rVSV-vectored vaccine expressing Ebola surface glycoprotein: interim results from the Guinea ring vaccination cluster-randomised trial. Lancet 2015; doi: 10.1016/S0140-6736(15)61117-5
Two preclinical successes for MERS Vaccines
Two vaccine candidates against Middle East Respiratory Syndrome (MERS) might advance to clinical trials. The first is an engineered antigen based on structural information about viral S glycoprotein. It was administered to mice and monkeys as a primer injection followed several weeks later by a booster. The vaccine elicited robust immune responses, and the immunized monkeys, in contrast to control animals, developed no lung abnormalities. The results were reported in Nature Communications.1
The second candidate is a collaborative effort of Inovio and researchers from U.S. and Canada. According to the study published in Science Translational Medicine,2 the DNA vaccine was 100% efficacious in monkeys and induced antibody production in camels, which are considered a major source of transmission to humans. Scientists want to advance this vaccine candidate to
1. Wang L, Shi W, Joyce MG, Modjarrad K, Zhang Y, Leung K, Lees CR, Zhou T, Yassine HM, Kanekiyo M, Yang ZY, Chen X, Becker MM, Freeman M, Vogel L, Johnson JC, Olinger G, Todd JP, Bagci U, Solomon J, Mollura DJ, Hensley L, Jahrling P, Denison MR, Rao SS, Subbarao K, Kwong PD, Mascola JR, Kong WP, Graham BS. Evaluation of candidate vaccine approaches for MERS-CoV. Nat Commun 2015; doi: 10.1038/ncomms8712
2. Muthumani K, Falzarano D, Reuschel EL, Tingey C, Flingai S, Villarreal DO, Wise M, Patel A, Izmirly A, Aljuaid A, Seliga AM, Soule G, Morrow M, Kraynyak KA, Khan AS, Scott DP, Feldmann F, LaCasse R, Meade-White K, Okumura A, Ugen KE, Sardesai NY, Kim JJ, Kobinger G, Feldmann H, Weiner DB. A synthetic consensus anti-spike protein DNA vaccine induces protective immunity against Middle East respiratory syndrome coronavirus in nonhuman primates. Sci Transl Med 2015; doi: 10.1126/scitranslmed.aac7462
Influenza Vaccination has an effect on elderly population
Vaccinating elderly against influenza would lead to decreased mortality and morbidity. According to a study published in Journal of the American Geriatrics Society,1 year-to-year variation in how well a vaccine strain matched the circulating strain correlated with number of deaths and hospitalizations of residents of U.S. nursing homes: the better the match, the lower the mortality, morbidity and healthcare costs.
The authors analyzed healthcare data between 2000 and 2009 and more than one million nursing-home residents. “This study evidences protection for an elderly population for whom vaccine efficacy has been questioned,” one of the authors Stefan Gravenstein of Brown University said in a press release “Annual vaccination is the only way to maximize the benefit of vaccine, no matter what the age.”
1. Pop-Vicas A, Rahman M, Gozalo PL, Gravenstein S, Mor V. Estimating the Effect of Influenza Vaccination on Nursing Home Residents' Morbidity and Mortality. J Am Geriatr Soc 2015; doi: 10.1111/jgs.13617
Single-dose Cholera Vaccination might be more effective than two doses during outbreaks
Administering oral cholera vaccine in one dose might save more lives than the recommended two-dose schedule in crisis situations, according to mathematical models published in PLOS Medicine.1 Researchers applied theoretical models to recent outbreaks in Haiti, Zimbabwe and Guinea and found that single-dose vaccination could have prevented 1.1-1.2 times more cases of cholera.
“When vaccine supplies are limited, one dose of vaccine is at least as good as two and it makes things logistically easier and cheaper to deliver. And in an outbreak, it is important to get as much vaccine out there as quickly as you can,” senior author Justin Lessler of Johns Hopkins Bloomberg School of Public Health said in a statement. Single-dose vaccination can also translate into more people being immunized, which promotes herd immunity.
Cholera is a major concern in the developing world, putting up to 1.5 billion people at risk. Linked to poor sanitation, it causes 100,000 deaths annually. An oral vaccine, licensed by the World Health Organization in 2011 and recommended for a two-dose regimen, is in relatively short supply.
1. Azman AS, Luquero FJ, Ciglenecki I, Grais RF, Sack DA, Lessler J. The Impact of a One-Dose versus Two-Dose Oral Cholera Vaccine Regimen in Outbreak Settings: A Modeling Study. PLOS Med 2015; 12:e1001867
Electronic reminders linked to increased uptake of Tdap Vaccine
The use of an automatic prompts system had a positive impact on the uptake of Tdap vaccine. A study published in American Journal of Public Health1 monitored immunization rates between 2008 and 2011, which tripled at five University of Michigan family clinics employing the system, and doubled during the same period at control clinics.
“This research shows how technology can be used to dramatically change the way preventive services are delivered and improve preventative health care,” senior author Grant Greenberg told the media.
1. Shultz CG, Malouin JM, Green LA, Plegue M, Greenberg GM. A Systems Approach to Improving Tdap Immunization Within 5 Community-Based Family Practice Settings: Working Differently (and Better) by Transforming the Structure and Process of Care. Am J Public Health 2015; doi: 10.2105/AJPH.2015.302739
HPV Vaccine coverage increased slightly among U.S. teens
The proportion of U.S. teenagers vaccinated against HPV increased in 2014, according to the CDC. 60% of girls aged 13-17 years and 42% of boys received at least one dose—increases of 3.3% and 8.1% respectively. At the same time, 40% of girls and 22% of boys received at least three doses—increases of 2.9% and 8.2% respectively. The survey was based on data for almost 21,000 subjects.
According to the CDC, cost is not the main barrier. Rather, healthcare providers are not recommending HPV vaccine as much as other immunizations. By comparison, 88% of teens received the Tdap vaccine.
HPV is a leading cause of sexually transmitted diseases, and persistent infection with some strains can lead to cervical cancer in women and other types of cancers in both sexes. 27,000 Americans are diagnosed with one of the cancers every year.
DTaP-IPV-Hib-HepB combination vaccine successful in a Phase 3 trial
A new hexavalent vaccine against diphtheria, tetanus, pertussis, polio, Haemophilus influenzae type b and hepatitis B is safe and efficacious in infants. An open-labeled Phase 3 clinical study compared the combination vaccine to separate administration of FDA-licensed vaccines, as included in the U.S. immunization schedule.
The trial, reported in Pediatrics,1 enrolled ˜1,500 infants. Both safety and immunogenicity were comparable between the two regimens; the combination-vaccine group reported slightly increased mild adverse events such as redness of injection site and fever.
A similar vaccine has been approved in Europe for more than a decade. Combining multiple vaccines in a single injection means fewer stressful pediatrician visits for infants and has additional benefits, as lead author Gary Marshall noted: “Hopefully, this vaccine combination will improve coverage rates. Studies show that when you use combination vaccines, more kids get vaccinated on time and by two years of age more are fully protected. When you make it easier, you get better coverage.”
1. Marshall GS, Adams GL, Leonardi ML, Petrecz M, Flores SA, Ngai AL, Xu J, Liu G, Stek JE, Foglia G, Lee AW. Immunogenicity, Safety, and Tolerability of a Hexavalent Vaccine in Infants. Pediatrics 2015; doi: 10.1542/peds.2014-4102
Positive Phase 2 results for a recombinant seasonal Influenza Vaccine
A quadrivalent recombinant seasonal influenza vaccine candidate (Novavax) was safe and immunogenic in a phase 2 clinical trial. No serious adverse events were reported in a sample of 400 healthy adults.
Unlike traditional egg-based influenza vaccines, recombinant VLP vaccine can be produced quickly and can reflect antigenic drift in the circulating strain. It has a potential to circumvent a mismatch between the vaccine and the virus, as happened last season.
The company plans to use the same technology for developing a H7N9 pandemic influenza vaccine, which received FDA fast-track designation in 2014.