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.

(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-yearolds, 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-yearolds, 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.

Notes
Disclaimers. 1) The authors and editors alone are responsible for the views expressed in this publication and they do not necessarily represent the views, decisions, or policies of the institutions with which they are affiliated; 2) The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of PATH or the World Health Organization (WHO) concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted and dashed lines on maps represent approximate border lines for which there may not yet be full agreement; 3) The mention of specific companies or of certain manufacturers' products does not imply that they are endorsed or recommended by PATH or the WHO in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters.
Supplement sponsorship. This article appears as part of the supplement "The Meningitis Vaccine Project: The Development, Licensure, Introduction, and Impact of a New Group A Meningococcal Conjugate Vaccine for Africa," sponsored by the Meningitis Vaccine Project through a grant from the Bill & Melinda Gates Foundation.
Potential conflicts of interest. M.-P. P. has received institutional grant support from PATH, Gavi the Vaccine Alliance, the Shefa Fund hosted by the Swiss Philanthropy Foundation, the National Philanthropic Trust, the Research Council of Norway, and the US Agency for International Development, and has received travel support from PATH and the Research Council of Norway. All other authors report no potential conflicts.