Serologic correlates of protection for evaluating the response to meningococcal vaccines

Meningococci cause serious disease worldwide and the organism remains the most common cause of bacterial meningitis in children and young adults. The only effective means of controlling disease is through vaccination. Although polysaccharide vaccines have been available for serogroup A, C, Y and W135 for many years, serogroup C polysaccharide-protein conjugate vaccines have only recently been licensed in many countries. Conjugate vaccines for combinations of serogroup A, C, Y and W135 are progressing through clinical trials and major efforts are being made to develop a safe and efficacious vaccine against serogroup B. To assess the quality of the immune response after vaccination, laboratory correlates of protection are needed. For serogroups A and C, serum bactericidal antibody is a well established predictor for protection but for serogroup B, other mechanisms besides serum bactericidal antibody may also be involved in conferring protection against disease. The serologic correlates of protection for evaluating the response to meningococcal vaccines are described in this review.     

Are vaccinated measles cases protected against severe disease?

ObjectivesWe aimed to estimate vaccine effectiveness against severe measles based on the number of vaccine doses administered and the time since last vaccination.Patients and methodsWe included measles cases aged at least 2 years and born since 1980 who were notified in France between 2006 and mid-2019. We considered two severity levels (moderate, severe) and calculated adjusted relative risks (aRR) using multinomial logistic regression.ResultsWe included 10,399 cases. The risk of severe measles in two-dose vaccine recipients was 71% (aRR = 0.29 [95%CI 0.12–0.72]) and 83% (aRR = 0.17 [95%CI 0.04–0.70]) lower than in unvaccinated cases, if the time since last dose was less or more than 15 years, respectively. The risk of moderate disease followed a similar pattern.ConclusionsTwo-dose measles vaccination provided long-term protection against severe cases, even after vaccine failures. These findings underscore the need for compliance to the recommended measles vaccination schedule to prevent severe cases.     

A method for evaluating and comparing immunisation schedules that cover multiple diseases: Illustrative application to the UK routine childhood vaccine schedule

BackgroundIn the UK, the childhood immunisation programme is given in the first 5 years of life and protects against 12 vaccine-preventable diseases. Recently, this programme has undergone changes with addition of vaccination against Meningitis B from September 2015 and the removal of the primary dose of protection against Meningitis C from July 2016. These hanges have direct impact on the associated diseases but in addition may induce indirect effects on the vaccines that are given simultaneously or later in the programme. In this work, we developed a novel formal method to evaluate the impact of vaccination changes to one aspect of the programme across an entire vaccine programme.MethodsFirstly, we combined transmission modelling (for four diseases) and historic data synthesis (for eight diseases) to project, for each disease, the disease burden at different levels of effective coverage against the associated disease. Secondly, we used a simulation model to determine the vector of effective coverage against each disease under three variations of the current childhood schedule. Combining these, we calculated the vector of disease burden across the programme under different scenarios, and assessed the direct and indirect effects of the schedule changes.ResultsThrough illustrative application of our novel framework to three scenarios of the current childhood immunisation programme in the UK, we demonstrated the feasibility of this unifying approach. For each disease in the programme, we successfully quantified the residual disease burden due to the change. For some diseases, the change was indirectly beneficial and reduced the burden, whereas for others the effect was adverse and the change increased the disease burden.ConclusionsOur results demonstrate the potential benefit of considering the programme-wide impact of changes to an immunisation schedule, and our framework is an important step in the development of a means for systematically doing so.     

Effectiveness of monovalent rotavirus vaccine in a high-income,predominant-use setting

Background and objectivesWe assessed monovalent rotavirus (RV1) vaccine effectiveness (VE) in a high-income setting with RV1 predominant use, and examined the burden of pediatric rotavirus gastroenteritis following the implementation of an RV1-only vaccination program.MethodsWe conducted active rotavirus gastroenteritis surveillance among children 8 weeks to <3 years of age at three hospitals. Participant information and vaccination histories were collected via parent/guardian interview and medical records. Stool specimens were tested for rotavirus; positive specimens were genotyped. The effect of increasing RV1 coverage on rotavirus prevalence was examined as a weekly time series via binomial regression with a log link function, using either categorical season or mean 2-dose rotavirus seasonal vaccine coverage as the exposure variable. As compared with RV1 vaccine formulation, rotavirus genotypes were classified as homotypic, partly-heterotypic, or heterotypic; prevalence of each was compared by season. A test-negative case-control design was used to examine RV1 VE against hospitalization or emergency visits.ResultsWe enrolled 866 participants in active surveillance; of these, 384 (44.3%) were eligible for VE analyses. After adjustment for season, we detected a 70.1% (95% CI: 21.9%, 88.6%) relative decrease in rotavirus prevalence in the 2013–14 season compared with 2012–13 season. On average, a 1% increase in ≥2-dose rotavirus coverage among children 1 year of age was associated with a 3.8% (95% CI: 1.8%, 5.8%) relative decrease in rotavirus prevalence. Rotavirus homotypic strain prevalence decreased, with 77% (95% CI: 68%, 89%) versus 8% (95% CI: 0%, 36%) prevalence during the 2011–12 and 2013–14 seasons, respectively. Adjusted 2-dose RV1 VE was 91.2% (95% CI: 61.6%, 98.0%).ConclusionsRV1 vaccine was highly effective to prevent rotavirus hospitalizations and emergency visits among children <3 years of age in a high-income setting with its predominant use. Our estimates were similar to high-income settings with concurrent RV1 and pentavalent vaccine use.     

Estimating the full public health value of vaccination

There is an enhanced focus on considering the full public health value (FPHV) of vaccination when setting priorities, making regulatory decisions and establishing implementation policy for public health activities. Historically, a therapeutic paradigm has been applied to the evaluation of prophylactic vaccines and focuses on an individual benefit-risk assessment in prospective and individually-randomized phase III trials to assess safety and efficacy against etiologically-confirmed clinical outcomes. By contrast, a public health paradigm considers the population impact and encompasses measures of community benefits against a range of outcomes. For example, measurement of the FPHV of vaccination may incorporate health inequity, social and political disruption, disruption of household integrity, school absenteeism and work loss, health care utilization, long-term/on-going disability, the development of antibiotic resistance, and a range of non-etiologically and etiologically defined clinical outcomes.Following an initial conference at the Fondation Mérieux in mid-2015, a second conference (December 2016) was held to further describe the efficacy of using the FPHV of vaccination on a variety of prophylactic vaccines. The wider scope of vaccine benefits, improvement in risk assessment, and the need for partnership and coalition building across interventions has also been discussed during the 2014 and 2016 Global Vaccine and Immunization Research Forums and the 2016 Geneva Health Forum, as well as in numerous publications including a special issue of Health Affairs in February 2016.The December 2016 expert panel concluded that while progress has been made, additional efforts will be necessary to have a more fully formulated assessment of the FPHV of vaccines included into the evidence-base for the value proposition and analysis of unmet medical need to prioritize vaccine development, vaccine licensure, implementation policies and financing decisions. The desired outcomes of these efforts to establish an alternative framework for vaccine evaluation are a more robust vaccine pipeline, improved appreciation of vaccine value and hence of its relative affordability, and greater public access and acceptance of vaccines.     

Bordetella pertussis epidemiology and evolution in the light of pertussis resurgence

Whooping cough, or pertussis, is resurgent in many countries world-wide. This is linked to switching from the use of whole cell vaccines to acellular vaccines in developed countries. Current evidence suggests that this has resulted in the earlier waning of vaccine-induced immunity, an increase in asymptomatic infection with concomitant increases in transmission and increased selection pressure for Bordetella pertussis variants that are better able to evade vaccine-mediated immunity than older isolates. This review discusses recent findings in B. pertussis epidemiology and evolution in the light of pertussis resurgence, and highlights the important role for genomics-based studies in monitoring B. pertussis adaptation.     

Public Acceptance and Willingness to Hepatitis A Vaccination in Children Aged 7-18 Years in Republic of Korea

Hepatitis A can cause serious illness among adolescents and adults with low vaccination coverage. Even though hepatitis A vaccine is one of the strong candidates for Korean national immunization program, adolescents aged older than 12 yr would not benefit. Our purpose was to assess the willingness and analyze the correlates of Korean mothers for hepatitis A (HepA) vaccination to develop strategies for HepA vaccination. A national telephone survey on 800 mothers with children aged 7-18 yr was conducted with random-digit dialing method. Sixty-two percent and 92% of the mothers reported that they were willing to HepA vaccination at current cost and at half of the current cost, respectively. However, at current cost, only 79% wished to vaccinate their child in an epidemic and 32% wished to vaccinate promptly. Having two or more children, not having future plans to send the child overseas, and low family income were significantly associated with not willing to HepA vaccination. Low perception of the susceptibility for hepatitis A and perception of the current cost as barrier increased the odds of unwillingness to vaccination at current cost and to prompt vaccination. The mothers'' willingness to HepA vaccination for the children aged 7-18 yr in Korea was not very high at current cost and associated socioeconomic status and health-belief. Targeted intervention or strategies are needed to increase the HepA vaccination rate among children in Korea.

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