Abstract

Despite advances in the development and introduction of vaccines against the major bacterial causes of meningitis, the disease and its long-term after-effects remain a problem globally. The Global Roadmap to Defeat Meningitis by 2030 aims to accelerate progress through visionary and strategic goals that place a major emphasis on preventing meningitis via vaccination. Global vaccination against Haemophilus influenzae type B (Hib) is the most advanced, such that successful and low-cost combination vaccines incorporating Hib are broadly available. More affordable pneumococcal conjugate vaccines are becoming increasingly available, although countries ineligible for donor support still face access challenges and global serotype coverage is incomplete with existing licensed vaccines. Meningococcal disease control in Africa has progressed with the successful deployment of a low-cost serogroup A conjugate vaccine, but other serogroups still cause outbreaks in regions of the world where broadly protective and affordable vaccines have not been introduced into routine immunization programs. Progress has lagged for prevention of neonatal meningitis and although maternal vaccination against the leading cause, group B streptococcus (GBS), has progressed into clinical trials, no GBS vaccine has thus far reached Phase 3 evaluation. This article examines current and future efforts to control meningitis through vaccination.

Highlights

  • The development and global introduction of low-cost vaccines to prevent Haemophilus influenzae type B (Hib) and pneumococcus has had a significant impact on meningitis and other disease manifestations caused by these pathogens

  • developing country vaccine manufacturers (DCVMs) have become the major suppliers of affordable Hib combination vaccines and the recent licensure and World Health Organization (WHO) prequalification of a 10-valent

  • (15–24 serotypes) pneumococcal conjugate vaccines (PCVs) are in development, though there are considerable manufacturing and licensing challenges for such vaccines and Low- and middle-income countries (LMICs) affordability is uncertain

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Summary

Introduction

Peak incidence: 9 to 14 years of age. Multi-dose RI schedules; first dose critical by 6 weeks to 2 mo. (4) Develop HibCV containing penta- and hexavalent combination vaccines. 1-dose primary in children 9 to 18 mo. Need for booster dose not yet determined. (1) Enhanced surveillance linking emergency vaccine requests to define meningitis burden. 2-dose primary/booster at 9 to 18 mo. RI–routine administration within EPI schedule; 2 SIA–supplementary immunization activity (mass campaign)

History and Status of Meningitis Vaccines
Early-Stage Meningitis Vaccine Development
Considerations
Schedule
Manufacturing
Nonclinical Assessment
Importance of Functional Assays
Phase 1 Clinical Trials
Phase 2 Clinical Trials
Late-Stage Clinical Development
Accelerating Vaccine Introduction to Prevent Meningitis
HibCV: Developing New Approaches to Increase Meningitis Vaccine Uptake
Defining Meningitis Burden to Justify Vaccine Introduction
Highly Directive Policies from Global Public Health Authorities
Structuring Vaccination Strategies for Success
Developing Innovative Vaccine Financing Options
Implications for New Meningitis Vaccines
Findings
Conclusions and Future Directions
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