Vaccine Efficacy and Vaccine Effectiveness

Mozambique introduced monovalent rotavirus vaccine (Rotarix^®) in September 2015. We evaluated the effectiveness of Rotarix^® under conditions of routine use in Mozambican children hospitalized with acute gastroenteritis (AGE). A test negative case-control analysis was performed on data collected during 2017–2019 from children <5 years old, admitted with AGE in seven sentinel hospital sites in Mozambique. Adjusted VE was calculated for ≥1 dose of vaccine vs. zero doses using unconditional logistic regression, where VE = (1 − aOR) × 100%. VE estimates were stratified by age group, AGE severity, malnutrition, and genotype. Among 689 children eligible for analysis, 23.7% were rotavirus positive (cases) and 76.3% were negative (controls). The adjusted VE of ≥1 dose in children aged 6–11 months was 52.0% (95% CI, −11, 79), and −24.0% (95% CI, −459, 62) among children aged 12–23 months. Estimated VE was lower in stunted than non-stunted children (14% (95% CI, −138, 66) vs. 59% (95% CI, −125, 91)). Rotavirus vaccination appeared moderately effective against rotavirus gastroenteritis hospitalization in young Mozambican children. VE point estimates were lower in older and stunted children, although confidence intervals were wide and overlapped across strata. These findings provide additional evidence for other high-mortality countries considering rotavirus vaccine introduction. Full article

Influenza is a vaccine preventable disease and vaccination remains the most effective method of controlling the morbidity and mortality of seasonal influenza, especially with respect to risk groups. To date, three types of influenza vaccines have been licensed: inactivated, live-attenuated, and recombinant haemagglutinin vaccines. Effectiveness studies allow an assessment of the positive effects of influenza vaccines in the field. The effectiveness of current influenza is suboptimal, being estimated as 40% to 60% when the vaccines strains are antigenically well-matched with the circulating viruses. This review focuses on influenza viruses and vaccines and the role of vaccine effectiveness studies for evaluating the benefits of influenza vaccines. Overall, influenza vaccines are effective against morbidity and mortality in all age and risk groups, especially in young children and older adults. However, the effectiveness is dependent on several factors such as the age of vaccinees, the match between the strain included in the vaccine composition and the circulating virus, egg-adaptations occurring during the production process, and the subject’s history of previous vaccination. Full article

For more than a century, epidemic meningococcal disease mainly caused by serogroup A Neisseria meningitidis has been an important public health problem in sub-Saharan Africa. To address this problem, an affordable meningococcal serogroup A conjugate vaccine, MenAfriVac^®, was developed specifically for populations in the African meningitis belt countries. MenAfriVac^® was licensed based on safety and immunogenicity data for a population aged 1–29 years. In particular, the surrogate markers of clinical efficacy were considered to be the higher immunogenicity and the ability to prime immunological memory in infants and young children compared to a polysaccharide vaccine. Because of the magnitude of serogroup A meningitis epidemics and the high morbidity and mortality burden, the World Health Organization (WHO) recommended the MenAfriVac^® deployment strategy, starting with mass vaccination campaigns for 1–29-year-olds to rapidly interrupt serogroup A person-to-person transmission and establish herd protection, followed by routine immunization of infants and toddlers to sustain protection and prevent epidemics. After licensure and WHO prequalification of MenAfriVac^®, campaigns began in December 2010 in Burkina Faso, Mali, and Niger. By the middle of 2011, it was clear that the vaccine was highly effective in preventing serogroup A carriage and disease. Post introduction meningitis surveillance revealed that serogroup A meningococcal disease had disappeared from all age groups, suggesting that robust herd immunity had been achieved. Full article

Observational studies are needed to demonstrate real-world vaccine effectiveness (VE) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outcomes. Our objective was to conduct a review of published SARS-CoV-2 VE articles, supplemented by preprints, during the first 6 months of COVID-19 vaccine availability. This review compares the effectiveness of completing the primary COVID-19 vaccination series against multiple SARS-CoV-2 disease presentations and disease severity outcomes in three population groups (general population, frontline workers, and older adults). Four hundred and seventy-one published articles and 47 preprints were identified. After title and abstract screening and full article review, 50 studies (28 published articles, 22 preprints) were included. VE results were reported for five COVID-19 vaccines and four combinations of COVID-19 vaccines. VE results for BNT162b2 were reported in 70.6% of all studies. Seventeen studies reported variant specific VE estimates; Alpha was the most common. This comprehensive review demonstrates that COVID-19 vaccination is an important tool for preventing COVID-19 morbidity and mortality among fully vaccinated persons aged 16 years and older and serves as an important baseline from which to follow future trends in COVID-19 evolution and effectiveness of new and updated vaccines. Full article

Yellow fever (YF) virus still represents a major threat in low resource countries in both South America and Africa despite the presence of an effective vaccine. YF outbreaks are not only due to insufficient vaccine coverage for insufficient vaccine supply, but also to the increase in people without history of vaccination living in endemic areas. Globalization, continuous population growth, urbanization associated with inadequate public health infrastructure, and climate changes constitute important promoting factors for the spread of this virus to tropical and subtropical areas in mosquito-infested regions capable of spreading the disease. In the present review, we focus on the origin of the virus and its transmission, representing two debated topics throughout the nineteenth century, going deeply into the history of YF vaccines until the development of the vaccine still used nowadays. Besides surveillance, we highlight the urgent need of routine immunization and vaccination campaigns associated to diverse and innovative mosquito control technologies in endemic areas for YF virus in order to minimize the risk of new YF outbreaks and the global burden of YF in the future. Full article

The coronavirus disease 2019 (COVID-19) pandemic has threatened global health and prompted the need for mass vaccination. We aimed to assess the efficacy and effectiveness of COVID-19 vaccines to prevent mortality and reduce the risk of developing severe disease after the 1st and 2nd doses. From conception to 28 June 2021, we searched PubMed, Cochrane, EBSCO, Scopus, ProQuest, Web of Science, WHO-ICTRP, and Google Scholar. We included both observational and randomized controlled trials. The pooled vaccine efficacy and effectiveness following vaccination, as well as their 95 percent confidence intervals (CI), were estimated using the random-effects model. In total, 22 of the 21,567 screened articles were eligible for quantitative analysis. Mortality 7 and 14 days after full vaccination decreased significantly among the vaccinated group compared to the unvaccinated group (OR = 0.10, ([95% CI, 0.04–0.27], I² = 54%) and (OR = 0.46, [95% CI, 0.35–0.61], I² = 0%), respectively. The probability of having severe disease one or two weeks after 2nd dose decreased significantly (OR = 0.29 [95% CI, 0.19–0.46], I² = 25%) and (OR = 0.08 [95% CI, 0.03–0.25], I² = 74%), respectively. The incidence of infection any time after the 1st and 2nd doses diminished significantly (OR = 0.14 [95% CI, 0.07–0.4], I² = 100%) and (OR = 0.179 [95% CI, 0.15–0.19], I² = 98%), respectively. Also, incidence of infection one week after 2nd dose decreased significantly, (OR = 0.04, [95% CI (0.01–0.2], I² = 100%). After meta-regression, the type of vaccine and country were the main predictors of outcome [non-mRNA type, ß = 2.99, p = 0.0001; country UK, ß = −0.75, p = 0.038; country USA, ß = 0.8, p = 0.02]. This study showed that most vaccines have comparable effectiveness, and it is purported that mass vaccination may help to end this pandemic. Full article

Rotavirus claims thousands of lives of children globally every year with a disproportionately high burden in low- and lower-middle income countries where access to health care is limited. Oral, live-attenuated rotavirus vaccines have been evaluated in multiple settings in both low- and high-income populations and have been shown to be safe and efficacious. However, the vaccine efficacy observed in low-income settings with high rotavirus and diarrheal mortality was significantly lower than that seen in high-income populations where rotavirus mortality is less common. Rotavirus vaccines have been introduced and rolled out in more than 112 countries, providing the opportunity to assess effectiveness of the vaccines in these different settings. We provide an overview of the efficacy, effectiveness, and impact of rotavirus vaccines, focusing on high-mortality settings and identify the knowledge gaps for future research. Despite lower efficacy, rotavirus vaccines substantially reduce diarrheal disease and mortality and are cost-effective in countries with high burden. Continued evaluation of the effectiveness, impact, and cost–benefit of rotavirus vaccines, especially the new candidates that have been recently approved for global use, is a key factor for new vaccine introductions in countries, or for a switch of vaccine product in countries with limited resources. Full article

Although measuring vaccine efficacy through the conventional phase III study design, randomized, double-blinded controlled trial serves as the “gold standard”, effectiveness studies, conducted in the context of a public health program, seek to broaden the understanding of the impact of a vaccine in a real world setting including both individual and population level impacts. Cholera is an acute diarrheal infection caused by the ingestion of food or water contaminated with the bacterium Vibrio cholerae. Since the 1980s, either killed or live oral cholera vaccines (OCVs) have been developed and efficacy and effectiveness studies have been conducted on OCV. Although the results of OCV effectiveness studies sometimes showed outliers, the tendency seen is for effectiveness of the vaccine used in public health settings to be somewhat higher than estimated in randomized controlled trials due to the influence of indirect herd protection. Efficacy and Effectiveness studies both generate important information about the vaccine performance characteristics and its impact when used in real world populations at risk for the disease. Full article

Human papillomavirus (HPV) is the most common sexually transmitted infection, with 15 HPV types related to cervical, anal, oropharyngeal, penile, vulvar, and vaginal cancers. However, cervical cancer remains one of the most common cancers in women, especially in developing countries. Three HPV vaccines have been licensed: bivalent (Cervarix, GSK, Rixensart, Belgium), quadrivalent (Merck, Sharp & Dome (Merck & Co, Whitehouse Station, NJ, USA)), and nonavalent (Merck, Sharp & Dome (Merck & Co, Whitehouse Station, NJ, USA)). The current HPV vaccine recommendations apply to 9 years old and above through the age of 26 years and adults aged 27–45 years who might be at risk of new HPV infection and benefit from vaccination. The primary target population for HPV vaccination recommended by the WHO is girls aged 9–14 years, prior to their becoming sexually active, to undergo a two-dose schedule and girls ≥ 15 years of age, to undergo a three-dose schedule. Safety data for HPV vaccines have indicated that they are safe. The most common adverse side-effect was local symptoms. HPV vaccines are highly immunogenic. The efficacy and effectiveness of vaccines has been remarkably high among young women who were HPV seronegative before vaccination. Vaccine efficacy was lower among women regardless of HPV DNA when vaccinated and among adult women. Comparisons of the efficacy of bivalent, quadrivalent, and nonavalent vaccines against HPV 16/18 showed that they are similar. However, the nonavalent vaccine can provide additional protection against HPV 31/33/45/52/58. In a real-world setting, the notable decrease of HPV 6/11/16/18 among vaccinated women compared with unvaccinated women shows the vaccine to be highly effective. Moreover, the direct effect of the nonavalent vaccine with the cross-protection of bivalent and quadrivalent vaccines results in the reduction of HPV 6/11/16/18/31/33/45/52/58. HPV vaccination has been shown to provide herd protection as well. Two-dose HPV vaccine schedules showed no difference in seroconversion from three-dose schedules. However, the use of a single-dose HPV vaccination schedule remains controversial. For males, the quadrivalent HPV vaccine possibly reduces the incidence of external genital lesions and persistent infection with HPV 6/11/16/18. Evidence regarding the efficacy and risk of HPV vaccination and HIV infection remains limited. HPV vaccination has been shown to be highly effective against oral HPV type 16/18 infection, with a significant percentage of participants developing IgG antibodies in the oral fluid post vaccination. However, the vaccines’ effectiveness in reducing the incidence of and mortality rates from HPV-related head and neck cancers should be observed in the long term. In anal infections and anal intraepithelial neoplasia, the vaccines demonstrate high efficacy. While HPV vaccines are very effective, screening for related cancers, as per guidelines, is still recommended. Full article