Exploitation of Neisseria meningitidis Group B OMV Vaccines Against N. gonorrhoeae to Inform the Development and Deployment of Effective Gonorrhea Vaccines

Have potential clues to an effective gonorrhea vaccine been lurking in international disease surveillance data for decades? While no clinically effective vaccines against gonorrhea have been developed we present direct and indirect evidence that a vaccine is not only possible, but may already exist. Experience from Cuba, New Zealand, and Canada suggest that vaccines containing Group B Neisseria meningitides outer membrane vesicles (OMV) developed to control type-specific meningococcal disease may also prevent a significant proportion of gonorrhea. The mechanisms for this phenomenon have not yet been elucidated but we present some strategies for unraveling potential cross protective antigens and effector immune responses by exploiting stored sera from clinical trials and individuals primed with a meningococcal group B OMV vaccine (MeNZB). Elucidating these will contribute to the ongoing development of high efficacy vaccine options for gonorrhea. While the vaccine used in New Zealand, where the strongest empirical evidence has been gathered, is no longer available, the OMV has been included in the multi component recombinant meningococcal vaccine 4CMenB (Bexsero) which is now licensed and used in numerous countries. Several lines of evidence suggest it has the potential to affect gonorrhea prevalence. A vaccine to control gonorrhea does not need to be perfect and modeling supports that even a moderately efficacious vaccine could make a significant impact in disease prevalence. How might we use an off the shelf vaccine to reduce the burden of gonorrhea? What are some of the potential societal barriers in a world where vaccine hesitancy is growing? We summarize the evidence and consider some of the remaining questions

Gonococcal vaccines: Public health value and preferred product characteristics; report of a WHO global stakeholder consultation, January 2019.

Renewed interest in developing vaccines against Neisseria gonorrhoeae has been sparked by the increasing threat of gonococcal antimicrobial resistance (AMR) and growing optimism that gonococcal vaccines are biologically feasible. Evidence suggests serogroup B Neisseria meningitidis vaccines might provide some cross-protection against N. gonorrhoeae, and new gonococcal vaccine candidates based on several approaches are currently in preclinical development. To further stimulate investment and accelerate development of gonococcal vaccines, greater understanding is needed regarding the overall value that gonococcal vaccines might have in addressing public health and societal goals in low-, middle-, and high-income country contexts and how future gonococcal vaccines might be accepted and used, if available. In January 2019, the World Health Organization (WHO) convened a multidisciplinary international group of experts to lay the groundwork for understanding the potential health, economic, and societal value of gonococcal vaccines and their likely acceptance and use, and for developing gonococcal vaccine preferred product characteristics (PPCs). WHO PPCs describe preferences for vaccine attributes that would help optimize vaccine value and use in meeting the global public health need. This paper describes the main discussion points and conclusions from the January 2019 meeting of experts. Participants emphasized the need for vaccines to control N. gonorrhoeae infections with the ultimate goals of preventing adverse sexual and reproductive health outcomes (e.g., infertility) and reducing the impact of gonococcal AMR. Meeting participants also discussed important PPC considerations (e.g., vaccine indications, target populations, and potential immunization strategies) and highlighted crucial research and data needs for guiding the value assessment and PPCs for gonococcal vaccines and advancing gonococcal vaccine development

The everchanging epidemiology of meningococcal disease worldwide and the potential for prevention through vaccination.

Neisseria meningitidis is a major cause of bacterial meningitis and septicaemia worldwide and is associated with high case fatality rates and serious life-long complications among survivors. Twelve serogroups are recognised, of which six (A, B, C, W, X and Y) are responsible for nearly all cases of invasive meningococcal disease (IMD). The incidence of IMD and responsible serogroups vary widely both geographically and over time. For the first time, effective vaccines against all these serogroups are available or nearing licensure. Over the past two decades, IMD incidence has been declining across most parts of the world through a combination of successful meningococcal immunisation programmes and secular trends. The introduction of meningococcal C conjugate vaccines in the early 2000s was associated with rapid declines in meningococcal C disease, whilst implementation of a meningococcal A conjugate vaccine across the African meningitis belt led to near-elimination of meningococcal A disease. Consequently, other serogroups have become more important causes of IMD. In particular, the emergence of a hypervirulent meningococcal group W clone has led many countries to shift from monovalent meningococcal C to quadrivalent ACWY conjugate vaccines in their national immunisation programmes. Additionally, the recent licensure of two protein-based, broad-spectrum meningococcal B vaccines finally provides protection against the most common group responsible for childhood IMD across Europe and Australia. This review describes global IMD epidemiology across each continent and trends over time, the serogroups responsible for IMD, the impact of meningococcal immunisation programmes and future needs to eliminate this devastating disease

Impact of meningococcal group B OMV vaccines, beyond their brief

Meningococcal group B outer membrane vesicle vaccines have been used widely in Cuba, New Zealand, and Brazil. They are immunogenic and initially assessed largely by their ability to induce serum bactericidal activity. Measures of efficacy indicate good protection against homologous strains in older children and adults. Effectiveness appears broader than predicted by immunogenicity and efficacy studies. The recent discovery that meningococcal group B OMVs may protect against the related Neisseria species N.gonorrhoeae suggests more to these interesting antigen collections than meets the eye. Currently there are two OMV-containing group B vaccines available, the new recombinant protein-based Bexsero® developed by Novartis and VA-MENGOC-BC® developed by the Finlay institute in Cuba. Also, a third group B vaccine based on two recombinant factor H binding proteins (Trumenba®, Pfizer), has recently been licenced but it does not include OMV. This commentary explores the population impact that group B OMV vaccines have had on meningococcal and gonorrhoea diseases. Given the heterologous effect against diverse strains of the meningococcus observed in older children and adults, and recent evidence to suggest moderate protection against gonorrhoea, there may be a role for these vaccines in programmes targeting adolescents and groups high at risk for both meningococcal disease and gonorrhoea

Pertussis Vaccination Failure in the New Zealand Pediatric Population: Study Protocol

Pertussis vaccines have been effective at reducing pertussis-associated morbidity and mortality. However, they have a complex array of limitations, particularly associated with the duration of protection against clinical disease and imperfect immunity (carriage and transmission). Little is known about risk factors for pertussis vaccination failure. Understanding pertussis vaccination failure risk is most important in the paediatric population. This study aims to investigate risk factors for pertussis vaccination failure in (1) infants between birth and six weeks of age born to mothers who received pertussis booster vaccinations during pregnancy and (2) infants after the completion of the primary series (approximately five months old) to four years old. This will be achieved in a two-step process for each study group. Pertussis vaccination failure cases will first be described using a case series study design, relevant case characteristics will be sourced from six national administrative datasets. The case series study results will help select candidate risk factors (hypothesis generating step) to be tested in the retrospective cohort study (hypothesis testing step). Pattern analysis will be used to investigate risk factor patterns in the cohort study. The identification of higher risk groups enables targeting strategies, such as additional doses, to better prevent pertussis disease

Vaccine decision making in New Zealand: a discrete choice experiment

Abstract Background Vaccine hesitancy is a significant threat to global health. A key part of addressing hesitancy is to ensure that public health messaging prioritises information that is considered important to the public. This study aimed to examine how different vaccine characteristics affect public preferences for vaccines in New Zealand, what trade-offs they are willing to make between different vaccine characteristics, and how their preferences are affected by their vaccine-related conspiracy beliefs and COVID-19 vaccination status. Methods An online discrete choice experiment (DCE) was designed to elicit individual preferences about vaccines using the 1000minds platform. Members of the general population of New Zealand aged ≥ 18 years were invited to complete the DCE. Participants were asked to indicate their preference between two options showing different combinations of vaccine characteristics. Data on sociodemographic characteristics were collected. Beliefs were measured using the vaccine conspiracy beliefs scale (VCBS) with scores ≥ 19 indicating strong vaccine-related conspiracy beliefs. The DCE was analysed using the PAPRIKA method (Potentially All Pairwise RanKings of all possible Alternatives) and preferences compared between respondents with high versus low VCBS scores and vaccinated versus unvaccinated respondents for COVID-19. Results A total of 611 respondents from 15 regions completed the DCE. Mean (SD) age was 45.9 (14.7) years with most having had 2 or more doses of the coronavirus vaccine (86%). Mean (SD) VCBS score was 18.5 (12.4) indicating moderate vaccine-related conspiracy beliefs. Risk of severe adverse effects was the most highly valued vaccine characteristic, followed by vaccine effectiveness and duration of protection. Vaccine origin and route of administration were ranked least important. Respondents scoring high on the VCBS placed less value on the effectiveness of vaccines but greater value on development time and total number of doses (p < 0.001). COVID-19 unvaccinated respondents ranked development time and total number of doses more highly than those vaccinated respondents (p < 0.001). Conclusions Risk of severe adverse effects, vaccine effectiveness and duration of protection were rated by the New Zealand public as the top three most important vaccine characteristics. This information is important for informing public health messaging to promote vaccine uptake and inform vaccine decision-making

Likelihood-based estimation and prediction for a measles outbreak in Samoa

Prediction of the progression of an infectious disease outbreak is important for planning and coordinating a response. Differential equations are often used to model an epidemic outbreak's behaviour but are challenging to parameterise. Furthermore, these models can suffer from misspecification, which biases predictions and parameter estimates. Stochastic models can help with misspecification but are even more expensive to simulate and perform inference with. Here, we develop an explicitly likelihood-based variation of the generalised profiling method as a tool for prediction and inference under model misspecification. Our approach allows us to carry out identifiability analysis and uncertainty quantification using profile likelihood-based methods without the need for marginalisation. We provide justification for this approach by introducing a new interpretation of the model approximation component as a stochastic constraint. This preserves the rationale for using profiling rather than integration to remove nuisance parameters while also providing a link back to stochastic models. We applied an initial version of this method during an outbreak of measles in Samoa in 2019–2020 and found that it achieved relatively fast, accurate predictions. Here we present the most recent version of our method and its application to this measles outbreak, along with additional validation

Reply to “Comment on Effectiveness of a Group B Outer Membrane Vesicle Meningococcal Vaccine in Preventing Hospitalization from Gonorrhea in New Zealand: A Retrospective Cohort Study, Vaccines, 2019, 1, 5; doi:10.3390/vaccines7010005”

Kenyon (2019) is correct to suggest that there is limited evidence of longer term effectiveness.[...