Meningitis Vaccine Project Research Articles

Implementation of the Meningitis Vaccine Project in Africa: lessons for vaccine implementation programs

Background The Meningitis Vaccine Project (MVP) was an international partnership that began in 2010 and focused on the development, testing, licensure, and widespread introduction of a conjugate vaccine with the promise of protecting millions of lives from group A meningococcal meningitis. To bridge gaps upstream of vaccine administration and in understanding the project’s planning, delivery and outcomes, the primary objective of this study was to delineate the barriers to and facilitators of sustainable implementation in an upstream context of the delivery of the MenAfriVac vaccine and to draw critical lessons for other vaccination programs. Methods We conducted a qualitative study with key project partners and leaders who worked on the MVP project. The interviewees were initially identified through a literature review and a search of publications and evaluations of the project. Eighteen key stakeholders were interviewed. The interviewees included individuals in the roles of implementation oversight, champion, partner, funder, and frontline implementer. The Consolidated Framework for Implementation Research (CFIR) informed the identification of a priori codes for the directed content analysis. Results There were multiple barriers and facilitators to implementing the vaccine under all five domains of the CFIR framework, including intervention characteristics, outer setting, inner setting, characteristics of individuals, and process. The most common domains mentioned by stakeholders that facilitated the success of the MVP were inner setting and process; specifically, three constructs were most representative—Tension for Change, Formally Appointed Implementation Leaders, and External Change Agents. Conclusions The tension for change—that is, the degree to which stakeholders perceive the current situation as intolerable or needing change— advocated by African leaders served as a crucial foundation for solid leadership for the MPV. The leadership came in the form of the project director and other formally appointed leaders, who could plan, engage and execute the project’s goals effectively. This leadership translated into consistent messaging, information sharing, and multiple levels of engagement with external change agents (including technical experts), which promoted a shared sense of readiness contributing to significant change investments in implementing MVP.

Global health Initiatives as a ‘Drunken Boat’: The Meningitis Vaccines Project Case Study

Based on an analysis of the Meningitis Vaccine Project (MVP), a public-private partnership (PPP) set up to introduce the MenAfriVac® vaccine in African countries, this article examines the failures of an accelerated disease control programme that targeted a highly infectious disease. I argue that the integration of MenAfriVac® into the World Health Organization’s (WHO) Expanded Programme on Immunisation had the effect of reinforcing inequalities in access, in particular during epidemic emergencies. I will also show how vaccine shortages during an outbreak in Niger led to political tensions and to the emergence of a parallel and unregulated ‘black market’ of vaccines.

Entrepreneurship and global health: activating the ecosystem and preventing disease

What kind of business models can be used to provide affordable healthcare on a viable basis? This paper points to new business models that attract participants in a value chain for innovation. Public-private partnerships can help to activate a supportive ecosystem and draw in participants to contribute to the innovation value chain. There are few economic incentives stimulating R&D for diseases of poverty. But policies with global reach have created new sources of financing to accelerate healthcare innovation in resource-poor settings. Combining resource-based theory of the firm with ecosystem analysis, we extend entrepreneurship theory beyond conventional applications and point to new business models to achieve global health objectives. We use case study evidence from the Meningitis Vaccine Project to show how entrepreneurial innovation can build resources and create value in the healthcare ecosystem.

Antibody kinetics following vaccination with MenAfriVac: an analysis of serological data from randomised trials

A meningococcal group A conjugate vaccine, PsA-TT (also known as MenAfriVac), was developed with the support of the Meningitis Vaccine Project. Around 280 million individuals aged 1-29 years have been immunised across the African meningitis belt. We analysed the kinetics of vaccine-induced antibody response and assessed the possible implications for duration of protection. We obtained data from two longitudinal studies done in The Gambia, Mali, and Senegal of antibody responses in 193 children aged 12-23 months and 604 participants aged 2-29 years following MenAfriVac vaccination. Antibodies were measured using two methods: group A serum bactericidal antibody (SBA) assay and group A-specific IgG ELISA. Data on antibody responses were analysed using a mixed-effects statistical model accounting for the mean response and variation in patterns of antibody kinetics. Determinants of antibody duration were investigated using regression analysis. In children age 12-23 months, the reduction in MenAfriVac-induced antibody levels assessed by SBA titres had two phases: with 97·0% (95% credible interval [CrI] 95·1-98·3) of the response being short lived and decaying within the first 6 months and the remainder being long lived and decaying with a half-life of 2690 days (95% CrI 1016-15 078). Antibody levels assessed by SBA titres in participants aged 2-29 years were more persistent, with 95·0% (85·7-98·1) of the response being short lived, and the long lived phase decaying with a half-life of 6007 days (95% CrI 2826-14 279). Greater pre-vaccination antibody levels were associated with greater immunogenicity following vaccination, as well as greater antibody persistence. Despite rapid antibody declines in the first phase, antibodies in the second phase persisted at SBA titres greater than 128. Although there is no strong evidence base for a correlate of protection against infection with Neisseria meningitidis serogroup A, we use an assumed SBA titre of 128 as a threshold of protection to predict that 20 years after vaccination with a single dose of MenAfriVac, vaccine efficacy will be 52% (29-73) in children vaccinated at age 12-23 months and 70% (60-79) in participants vaccinated at age 2-29 years. Population-level immunity induced by routine vaccination with the Expanded Programme on Immunization is predicted to persist at levels sufficient to confer more than 50% protection over a 20-year time period. Further increases in population-level immunity could be obtained via mass campaigns or by delaying the age of vaccination through the Expanded Programme on Immunization. However, the benefits of such a strategy would need to be weighed against the risks of leaving young children unvaccinated for longer. Meningitis Vaccine Project and Institut Pasteur.

Lessons from the Meningitis Vaccine Project.

From 2001 to 2017 the Meningitis Vaccine Project (MVP), a Gates Foundation funded partnership between PATH and the World Health Organization (WHO), successfully developed, tested, licensed, and introduced an affordable new Group A meningococcal conjugate vaccine, MenAfriVac, in sub-Saharan Africa. The vaccine was well received, and from 2010 to 2016, over 260 million Africans have received a dose of the vaccine in campaigns largely directed at 1–29-year olds. The public health impact has been dramatic with the elimination of Group A meningococcal infections wherever the vaccine has been used at public health scale. Over its 16-year life span, MVP faced many challenges, and lessons were learned that may be of interest to other groups seeking to develop vaccine products for resource-poor countries. We have chosen to highlight six elements that were keys to the success of the project: (a) country and African regional engagement during all phases of the project; (b) the evolution of the WHO/PATH partnership; (c) funding the introduction of MenAfriVac in meningitis belt countries; (d) regulatory challenges; (e) clinical trials in Africa and India; and (f ) the realities of vaccine development partnerships.

Ambiguous Capture: Collaborative Capitalism and the Meningitis Vaccine Project

ABSTRACTThe primary health care approach advanced at Alma Ata to address social determinants of health was replaced by selective health care a year later at Bellagio. Subsequently, immunization was endorsed as a cost-effective technical intervention to combat targeted infectious diseases. Multilateral efforts to collaborate on immunization as a universal public health good ambiguously capture the interests of the world’s governments as well as private, public, and not-for-profit institutions. Global assemblages of scientists, governments, industry and nongovernmental organizations now work in public-private partnerships to develop and make essential vaccines accessible, with vaccines marketed as single fix solutions for global health. Drawing from ethnographic fieldwork in France and Burkina Faso that followed the development, regulation, and implementation of the group A meningococcal conjugate vaccine for sub-Saharan Africa, in this article I describe events during and after the development of MenAfriVac. A technological success narrative steeped in collaborative capitalist rhetoric disguises neglected health care systems.

The Evolution of the Meningitis Vaccine Project.

Background. In 2001, the Meningitis Vaccine Project (MVP) was tasked to develop, test, license, and introduce a group A meningococcal (MenA) conjugate vaccine for sub-Saharan Africa. African public health officials emphasized that a vaccine price of less than US$0.50 per dose was necessary to ensure introduction and sustained use of this new vaccine.Methods. Initially, MVP envisioned partnering with a multinational vaccine manufacturer, but the target price and opportunity costs were problematic and formal negotiations ended in 2002. MVP chose to become a “virtual vaccine company,” and over the next decade managed a network of public–private and public–public partnerships for pharmaceutical development, clinical development, and regulatory submission. MVP supported the transfer of key know-how for the production of group A polysaccharide and a new conjugation method to the Serum Institute of India, Ltd, based in Pune, India. A robust staff structure supported by technical consultants and overseen by advisory groups in Europe and Africa ensured that the MenA conjugate vaccine would meet all international standards.Results. A robust project structure including a team of technical consultants and 3 advisory groups in Europe and Africa ensured that the MenA conjugate vaccine (PsA-TT, MenAfriVac) was licensed by the Drug Controller General of India and prequalified by the World Health Organization in June 2010. The vaccine was introduced in Burkina Faso, Mali, and Niger in December 2010.Conclusions. The development, through a public–private partnership, of a safe, effective, and affordable vaccine for sub-Saharan Africa, PsA-TT, offers a new paradigm for the development of vaccines specifically targeting populations in resource-poor countries.

Challenges and Opportunities While Developing a Group A Meningococcal Conjugate Vaccine Within a Product Development Partnership: A Manufacturer's Perspective From the Serum Institute of India.

Background. In 2002, the Meningitis Vaccine Project (MVP) chose the Serum Institute of India, Ltd (SIIL), as its manufacturing partner to establish a product development partnership (PDP) with the Meningitis Vaccine Project (MVP). MVP was a collaboration between PATH and the World Health Organization (WHO) to develop meningococcal conjugate vaccines for sub-Saharan Africa.Method. From the outset, SIIL recognized that a partnership with MVP carried some risk but also offered important opportunities for accessing new conjugate vaccine technology and know-how. Over 3 years, SIIL successfully accepted technology transfer for the group A meningococcal polysaccharide from SynCo Bio Partners and a conjugation method from the US Food and Drug Administration.Results. SIIL successfully scaled up production of a group A meningococcal conjugate vaccine that used SIIL tetanus toxoid as the carrier protein. Phase 1 studies began in India in 2005, followed by phase 2/3 studies in Africa and India. A regulatory dossier was submitted to the Indian authorities in April 2009 and WHO in September 2009. Export license was granted in December 2009, and WHO prequalification was obtained in June 2010. Vaccine was introduced at public scale in Burkina Faso that December. The group A meningococcal conjugate vaccine was named MenAfriVac, and is the first internationally qualified vaccine developed outside of big pharma.Conclusions. The project proved to be a sound investment for SIIL and is a concrete example of the potential for PDPs to provide needed products for resource-poor countries.

Ethical Challenges and Lessons Learned During the Clinical Development of a Group A Meningococcal Conjugate Vaccine.

Background. The group A meningococcal vaccine (PsA-TT) clinical development plan included clinical trials in India and in the West African region between 2005 and 2013. During this period, the Meningitis Vaccine Project (MVP) accumulated substantial experience in the ethical conduct of research to the highest standards.Methods. Because of the public–private nature of the sponsorship of these trials and the extensive international collaboration with partners from a diverse setting of countries, the ethical review process was complex and required strategic, timely, and attentive communication to ensure the smooth review and approval for the clinical studies. Investigators and their site teams fostered strong community relationships prior to, during, and after the studies to ensure the involvement and the ownership of the research by the participating populations. As the clinical work proceeded, investigators and sponsors responded to specific questions of informed consent, pregnancy testing, healthcare, disease prevention, and posttrial access.Results. Key factors that led to success included (1) constant dialogue between partners to explore and answer all ethical questions; (2) alertness and preparedness for emerging ethical questions during the research and in the context of evolving international ethics standards; and (3) care to assure that approaches were acceptable in the diverse community contexts.Conclusions. Many of the ethical issues encountered during the PsA-TT clinical development are familiar to groups conducting field trials in different cultural settings. The successful approaches used by the MVP clinical team offer useful examples of how these problems were resolved.Clinical Trials Registration. ISRCTN17662153 (PsA-TT-001); ISRTCN78147026 (PsA-TT-002); ISRCTN87739946 (PsA-TT-003); ISRCTN46335400 (PsA-TT-003a); ISRCTN82484612 (PsA-TT-004); CTRI/2009/091/000368 (PsA-TT-005); PACTR ATMR2010030001913177 (PsA-TT-006); PACTR201110000328305 (PsA-TT-007).

Documenting the Results of a Successful Partnership: A New Meningococcal Vaccine for Africa.

The Meningitis Vaccine Project, a partnership between the World Health Organization (WHO) and PATH, an international nonprofit organization, existed from 21 June 2001 to 31 December 2014. The project had a single goal: the development, licensure, and introduction of a group A meningococcal conjugate vaccine in sub-Saharan Africa. It was successful and resulted in the WHO prequalification of 2 products, a PsA-TT 10-µg vaccine for use in mass vaccination campaigns among 1- to 29-year-olds, and a 5-µg vaccine for use in routine immunization programs among children <2 years of age. Since 2010, the 10-µg vaccine has been used to immunize 1- to 29-year-olds in large vaccination campaigns in countries of the sub-Saharan African meningitis belt. WHO has recommended introduction of the 5-µg vaccine into the routine childhood immunization program within 1–5 years following campaign completion. Many lessons have been learned through the development, testing, and introduction of MenAfriVac (PsA-TT), and this collection of articles is an attempt at documenting results and lessons learned. Grouping articles on a single theme is an arbitrary exercise; the editors have chosen to group the purely serologic articles in a separate section. The initial section in general follows the historical procession from an idea that began in 1998 to the assessment of the impact of MenAfriVac introduction. A collection of 4 safety articles bridges sections 1 and 2. The editors have chosen to be inclusive so that readers may have a detailed view of the many steps required to develop and license a new vaccine. In addition to the group of articles that were included, there are previous publications, in particular, those describing the results of clinical trials using PsA-TT. Many of development steps were used as important training opportunities. The article by Dellepiane et al is an excellent description of the regulatory challenges facing companies that wish to license a new vaccine [1]. The use of a fast track for prequalification and WHO's accelerated process for country registration greatly facilitated getting the vaccine properly registered. Diomande's article on pharmacovigilance is particularly important given the all-too-common assertion that pharmacovigilance cannot be done in sub-Saharan Africa [2]. Similarly, the article by Wak et al clearly documents the safety of PsA-TT when given to pregnant women [3]. More than 217 million doses have been given from 2010 through December 2014, and group A Neisseria meningitidis has disappeared wherever the vaccine has been used. The vaccine's impact is well summarized in Diomande's article that amply documents vaccine impact, particularly in Chad and Burkina Faso [4]. Diallo et al describe the antibody persistence in 2- to 29-year-olds, demonstrating that antibodies at 1 and 4 years following immunization with PsA-TT persist significantly better than following polysaccharide vaccination. Four years following a single dose of PsA-TT, most individuals still had protective antibody titers [5]. Tapia et al demonstrated that in 12- to 23-month-old Africans, antibody levels remained significantly above baseline up to 5 years following vaccination, with the majority of children remaining protected [6]. An added benefit of immunizing with PsA-TT is the carrier protein tetanus toxoid (TT) itself. PsA-TT has been shown to generate robust tetanus serologic responses in 1- to 29-year-olds, similar to those expected after a booster dose of TT [7]. Of note, neonatal cases of tetanus have fallen by 25% in countries that completed PsA-TT campaigns in 1- to 29-year-olds. No vaccine-related serious adverse events (SAEs) occurred during the 3 months of follow-up of 4004 healthy Malians vaccinated with a single dose of PsA-TT; in addition, rates of systemic reactions, adverse events, and SAEs were similar to those in the polysaccharide control vaccine group and were considered unrelated to vaccination [8]. This collection of articles offers a unique look into an important public health problem that has been controlled. Nonetheless, the need for continued enhanced meningitis surveillance in Africa remains a high priority because of the threat that 1 or more non-A meningococcal strains in Africa will assume epidemic proportions. PsA-TT's success has generated a new confidence that over time, and with the development and use of affordable polyvalent meningococcal conjugate vaccines, meningococcal disease may well be eliminated from sub-Saharan Africa.

Community Perspectives Associated With the African PsA-TT (MenAfriVac) Vaccine Trials.

Background. The Meningitis Vaccine Project (MVP) was established to address epidemic meningitis as a public health problem in sub-Saharan Africa and, to that end, worked to develop a group A meningococcal conjugate vaccine, PsA-TT.Methods. Experiences in 4 clinical trial sites are described. Culturally sensitive collaborative strategies were adopted to manage acceptable communication methods, peculiarities with the consent process, participant medical issues, community care, and death.Results. The clinical trials were completed successfully through community acceptance and active community collaboration. The trials also strengthened the capacities in the participating communities, and actively worked to resolve community problems.Conclusions. The understanding and integration of sociocultural realities of communities were major assets in the conduct and acceptance of these trials. MVP succeeded in these sites and provided a sound example for future clinical studies in Africa.Clinical Trials Registration. ISRTCN78147026 (PsA-TT 002); ISRCTN87739946 (PsA-TT 003); ISRCTN82484612 (PsA-TT 004); PACTR ATMR2010030001913177 (PsA-TT 006); and PACTR201110000328305 (PsA-TT 007).

Technical Development of a New Meningococcal Conjugate Vaccine.

Background. Group A Neisseria meningitidis has been a major cause of bacterial meningitis in the sub-Saharan region of Africa in the meningitis belt. Neisseria meningitidis is an encapsulated pathogen, and antibodies against the capsular polysaccharide are protective. Polysaccharide–protein conjugate vaccines have proven to be highly effective against several different encapsulated bacterial pathogens. Purified polysaccharide vaccines have been used to control group A meningococcal (MenA) epidemics with minimal success.Methods. A monovalent MenA polysaccharide–tetanus toxoid conjugate was therefore developed. This vaccine was developed by scientists working with the Meningitis Vaccine Project, a partnership between PATH and the World Health Organization.Results. A high-efficiency conjugation method was developed in the Laboratory of Bacterial Polysaccharides in the Center for Biologics Evaluation and Research and transferred to the Serum Institute of India, Ltd, which then developed methods for purification of the group A polysaccharide and used its tetanus toxoid as the carrier protein to produce the now-licensed, highly effective MenAfriVac conjugate vaccine.Conclusions. Although many years of application of meningococcal polysaccharide vaccines have had minimal success in preventing meningococcal epidemics in the meningitis belt of Africa, our collaborative efforts to develop a MenA conjugate vaccine yielded a safe and highly effective vaccine.

Influence of Age on Antibody Response and Persistence Following Immunization With MenAfriVac.

Background. A meningococcal group A conjugate vaccine, PsA-TT (MenAfriVac), developed through the Meningitis Vaccine Project and manufactured by the Serum Institute of India, Ltd, was tested in multiple clinical trials conducted mainly in Africa. The impact of age at which subjects were vaccinated on immune response and persistence postimmunization with PsA-TT was the main focus of the current analysis.Methods. Subjects who were vaccinated with a single dose of 10 µg of PsA-TT at 12–23 months or 22–33 months of age in study A conducted in Mali and The Gambia; at 2–10 years, 11–17 years, or 18–29 years of age in study B conducted in Mali, The Gambia, and Senegal; and at 14–18 weeks, 9–12 months, or 12–18 months of age in study C conducted in Ghana are included in the current analysis. Immunogenicity was measured by group A serum bactericidal antibody (SBA) titer with baby rabbit complement.Results. Significant differences in SBA titers were found among the age groups in studies B and C both 28 days and 1 year postimmunization. A significant difference in SBA titers between age groups 12–23 months and 22–33 months was only observed 1 year postimmunization in study A. Antibody titers remained at similar levels from 1 to 2 years postimmunization for subjects vaccinated at 12–23 months in study A and at 9–12 months or 12–18 months of age in study C.Conclusions. Subjects immunized at different ages had different postimmunization immune responses as measured by SBA titers. Toddlers tended to have higher immune responses than infants. This pattern persisted at least 1 year postimmunization.Clinical Trials Registration. ISRCTN78147026 (study A), ISRCTN87739946 (study B), and ISRCTN82484612 (study C).

From Epidemic Meningitis Vaccines for Africa to the Meningitis Vaccine Project.

Background. Polysaccharide vaccines had been used to control African meningitis epidemics for >30 years but with little or modest success, largely because of logistical problems in the implementation of reactive vaccination campaigns that are begun after epidemics are under way. After the major group A meningococcal meningitis epidemics in 1996–1997 (250 000 cases and 25 000 deaths), African ministers of health declared the prevention of meningitis a high priority and asked the World Health Organization (WHO) for help in developing better immunization strategies to eliminate meningitis epidemics in Africa.Methods. WHO accepted the challenge and created a project called Epidemic Meningitis Vaccines for Africa (EVA) that served as an organizational framework for external consultants, PATH, the US Centers for Disease Control and Prevention (CDC), and the Bill & Melinda Gates Foundation (BMGF). Consultations were initiated with major vaccine manufacturers. EVA commissioned a costing study/business plan for the development of new group A or A/C conjugate vaccines and explored the feasibility of developing these products as a public–private partnership. Representatives from African countries were consulted. They confirmed that the development of conjugate vaccines was a priority and provided information on preferred product characteristics. In parallel, a strategy for successful introduction was also anticipated and discussed.Results. The expert consultations recommended that a group A meningococcal conjugate vaccine be developed and introduced into the African meningitis belt. The results of the costing study indicated that the “cost of goods” to develop a group A – containing conjugate vaccine in the United States would be in the range of US$0.35–$1.35 per dose, depending on composition (A vs A/C), number of doses/vials, and presentation. Following an invitation from BMGF, a proposal was submitted in the spring of 2001.Conclusions. In June 2001, BMGF awarded a grant of US$70 million to create the Meningitis Vaccine Project (MVP) as a partnership between PATH and WHO, with the specific goal of developing an affordable MenA conjugate vaccine to eliminate MenA meningitis epidemics in Africa. EVA is an example of the use of WHO as an important convening instrument to facilitate new approaches to address major public health problems.

A Vaccine Meets Its Promise: Success in Controlling Epidemic Meningitis in Sub-Saharan Africa.

Over the last 4 years, a remarkable public health success has unfolded in Africa. The field introduction of a new group A meningococcal conjugate vaccine, PsA-TT (MenAfriVac), has been a stunning success, with the virtual disappearance of group A meningococcal meningitis in sub-Saharan Africa. The effort began with a plea from African ministers of health to “do something” after the dreadful 1996–1997 group A meningococcal epidemic with >250 000 reported cases. The World Health Organization (WHO) convened a series of international meetings where experts recommended that a new meningococcal group A conjugate vaccine be developed for Africa. In 2001, the Bill & Melinda Gates Foundation awarded a grant of US$70 million to create the Meningitis Vaccine Project as a partnership between PATH and WHO, with the single goal of developing, licensing, and introducing at public health scale a group A meningococcal conjugate vaccine for sub-Saharan Africa, manufactured at the Serum Institute of India, Ltd. Using an innovative vaccine development model that paid close attention to product specifications to facilitate use of the vaccine in Africa (fewest doses required for compliance; relative stability outside cold chain) and affordability (less than US$0.50 per dose), the new vaccine, PsA-TT, was licensed by the Drug Controller General of India in December 2009 and prequalified by WHO in June 2010 [1]. The vaccine was introduced in Burkina Faso, Mali, and Niger in December 2010 and was enthusiastically accepted. By the end of that month, almost 20 million persons aged 1–29 years had been vaccinated, and the following epidemic season showed a dramatic reduction in group A meningococcal disease in all 3 countries. Vaccination campaigns have continued, and as of the end of 2014, >217 million Africans have been immunized in 15 countries. The vaccine has been shown to be safe and has generated herd protection, with control and near-elimination of group A meningococcal disease wherever it has been used [2–4]. The vaccine was further evaluated in infants and young children to prepare for its use in the Expanded Programme on Immunization (EPI), an essential step to ensure that subsequent newborn cohorts are protected and that the public health benefits continue. With study results showing safety and strong immunogenicity of a single dose at the age of 9 months and following the WHO Strategic Advisory Group of Experts on Immunization recommendations of October 2014, the vaccine is now gradually introduced as a new EPI antigen in meningitis belt countries [5]. Participants in this effort have prepared a series of manuscripts that detail the many technical, epidemiologic, and public health steps that were associated with the development, introduction, and evaluation of this vaccine. The success of the project is a testimonial to the potential of public/private partnerships to develop needed vaccines that, when introduced, can have major impact to solve important public health problems. It is our hope that the lessons learned from this endeavor will inform similar future public health initiatives.

CNS infections in 2014: guns, germs, and will

CNS infections in 2014: guns, germs, and will

HHS--supporting global immunization through policies, programs, and partnerships.

HHS--supporting global immunization through policies, programs, and partnerships.

Meningococcal Conjugate Vaccine Effective in Chad

Regions of Africa have large, seasonal epidemics of meningococcal meningitis, usually serogroup A. In Chad, epidemics have persisted despite the use of polysaccharide vaccine given in response to outbreaks. Conjugate vaccines offer potential advantages — immunogenicity in young children, induction of immunologic memory, and prevention of pharyngeal carriage. An affordable, monovalent serogroup A polysaccharide–tetanus toxoid conjugate vaccine (PsA-TT) was developed through the Meningitis Vaccine Project, a public–private partnership. Based …

Editorial Commentary: The Endgame for Serogroup A Meningococcal Disease in Africa?

Editorial Commentary: The Endgame for Serogroup A Meningococcal Disease in Africa?

Conducting vaccine clinical trials in sub-Saharan Africa: Operational challenges and lessons learned from the Meningitis Vaccine Project

Group A Neisseria meningitidis epidemics have been an important and unresolved public health problem in sub-Saharan Africa for over a century. The Meningitis Vaccine Project (MVP) was established in 2001 with the goal of developing, testing, licensing, and introducing an affordable group A meningococcal conjugate vaccine for Africa. A monovalent group A conjugate vaccine, MenAfriVac™, was developed at the Serum Institute of India Ltd. and tested in clinical trials at multiple trial sites in sub-Saharan African countries.The setup and successful conduct of ICH-GCP standard vaccine trials across multiple trial sites located in low-resource settings are challenging. We describe the main operational issues encountered in three randomized, observer-blind, active controlled studies to evaluate the safety and immunogenicity of MenAfriVac™. The studies were conducted in parallel among 2700 subjects aged between 2 months and 29 years of age enrolled across four trial sites located in Mali, The Gambia, Senegal, and Ghana between September 2006 and August 2009.Many important lessons were learned during the preparation, setup, and implementation of the Meningitis Vaccine Project clinical program. They are summarized here to help vaccine development programs identify efficient pathways for successful implementation of clinical trials in low-resource settings.