An international team of researchers says the results of one of three phase 3 randomised clinical trials show promise and reinforces the use of a vaccine that protects against five strains of meningitis in routine childhood immunisation programmes in countries with a high burden of meningococcal disease.
The trial, published in The Lancet, was conducted in babies and toddlers aged nine and 15 months in Mali, and aimed to assess the safety and immunogenicity of NmCV-5, a single-dose, five-valent meningococcal conjugate vaccine, compared with the quadrivalent (four-strain) MenACWY-TT vaccine when co-administered with routine childhood vaccines.
CIDRAP reports that previous trials have shown that NmCV-5, which targets Neisseria meningitidis serogroups A, C, Y, W and X, is safe and produces a robust immune response against all five serotypes in children older than 12 months, and adults.
This was one of three phase 3 trials planned to assess the vaccine in children under 12-months-old, and provide evidence to incorporate the vaccine into routine immunisation programmes for infants.
Mali is one of the 26 countries in a region of sub-Saharan Africa known as the meningitis belt, where rates of meningitis incidence are high and large-scale epidemics occur every five to 12 years. Because of the rapid onset of invasive bacterial meningitis, and the difficulties in accessing healthcare in the region, death rates can surpass 15%.
Although the introduction of the monovalent MenAfriVac vaccine in 2010 has led to the virtual elimination of meningitis caused by serogroup A disease, the region still experiences outbreaks and epidemics of meningitis primarily caused by serogroups C, W and X.
Developed by Serum Institute of India and PATH, NmCV-5 is the first vaccine to include serogroup X.
“This study represents a necessary evaluation of this vaccine to satisfy the conditions for its use within the Expanded Programme on Immunisation (EIP) and protect new birth cohorts,” the investigators wrote.
NmCV-5 safe, non-inferior to MenACWY
Between 24 March and 15 August 2022, the investigators enrolled and randomised 1 200 infants who had completed their EIP vaccines to receive a meningitis vaccine at either nine months (600 infants) or 15 months (600 infants) of age. In both groups, the participants were randomised 2:1 to receive either NmCV-5 or MenACWY-TT. The primary end point of the trial was seroprotective response for all five serotypes in both age-groups, with a non-inferiority margin of –10%.
In both age-groups, the difference in seroprotective responses for NmCV-5 were non-inferior to MenACWY-TT. In the nine-month-old group, the difference in seroprotection prevalence for NmCV-5 relative to MenACWY was 0.0% (95% confidence interval [CI], –1.0% to 2.0%) for serogroup A, –0.5% (95% CI, –2.3% to 1.9%) for serogroup C, –3.0% (95% CI, –6.3% to 0.8%) for serogroup W, and –3.0% (95% CI, –5.4% to –0.4%) for serogroup Y.
For serogroup X, non-inferiority was assessed relative to seroprotection for serogroup W in participants who received MenACWY-TT, with a difference of 2.3% (95% CI, 0.3% to 4.7%).
Among the participants who received NmCV-5 at 15 months relative to participants who received MenACWY-TT, the difference in the prevalence of seroprotection was 0.8% (95% CI, –0.6% to 3.7%) for serogroup A, –0.8% (95% CI, –3.3% to 2.5%) for serogroup C, 0.3% (95% CI, –1.8% to 3.5%) for serogroup W, and 1.4% (95% CI, –0.6% to 4.8%) for serogroup Y. For serogroup X, non-inferiority was assessed in relation to seroprotection for serogroup Y in participants who received MenACWY-TT, with a difference of 1.9% (95% CI, 0.0% to 4.4%).
A total of six adverse events were recorded in the trial, but none was related to vaccination.
The study authors say the results suggest NmCV-5 should be introduced in sub-Saharan Africa for further elimination of meningococcal disease.
‘Reassuring evidence’
“This critical clinical study provides reassuring evidence that this pentavalent vaccine can be safely and effectively given along with other routine immunisations, which makes it far easier to curtail invasive meningococcal disease and potentially save tens of thousands of lives,” said trial protocol Chair Wilbur Chen, MD, of the University of Maryland School of Medicine’s Centre for Vaccine Development and Global Health.
The results of the trial were included in the evidence base for the World Health Organisation’s October 2023 decision to recommend that countries in the meningitis belt introduce NmCV-5 into their routine immunisation programmes. In April 2024, Nigeria became the first country to roll out the vaccine.
In an accompanying commentary, experts from the University of Cambridge and Centre Suisse de Recherches Scientifique en Cote d’Ivoire say the results provide hope that the NmCV-5 vaccine can do for serogroups C, W, Y and X what the MenA conjugate vaccine did for serogroup A. They also note that the vaccine’s affordability – approximately $3 per dose – could ensure its use at a public health scale.
“NmCV-5 can revolutionise meningitis control in Africa, and efforts now must ensure that it is used at a scale that enables this effect,” they wrote.
Study details
Safety and immunogenicity of a pentavalent meningococcal conjugate vaccine targeting serogroups A, C, W, Y, and X when co-administered with routine childhood vaccines at ages 9 months and 15 months in Mali: a single-centre, double-blind, randomised, controlled, phase 3, non-inferiority trial
Fatoumata Diallo, Fadima Haidara, Milagritos Tapia et al.
Published in The Lancet on 11 March 2025
Summary
Background
Invasive meningococcal disease is a devastating public health problem for the African meningitis belt. We assessed the safety and immunogenicity of a pentavalent meningococcal conjugate vaccine targeting serogroups A, C, Y, W, and X (NmCV-5) relative to a licensed, quadrivalent meningococcal conjugate vaccine (MenACWY-TT) when co-administered with routine childhood vaccines at ages 9 months and 15 months.
Methods
In this single-centre, double-blind, randomised, controlled, phase 3, non-inferiority trial, children aged 9–11 months who had completed their local infant Expanded Program on Immunisation (EPI) vaccines were recruited at the Centre pour le Développement des Vaccins in Bamako, Mali. Participants were randomly assigned (1:1·2) at their 9-month EPI visits to receive a meningococcal vaccine at either their 9-month or 15-month EPI vaccination visits. At each participant's designated EPI visit, they were randomly assigned a second time (2:1) to receive either NmCV-5 or MenACWY-TT. Study vaccines and designated EPI vaccines were prepared and administered by assigned unmasked study personnel. Parents or guardians, investigators, and all other trial staff were masked to meningococcal vaccine assignments. The meningococcal vaccines were co-administered with a measles and rubella vaccine (first dose) and a yellow fever vaccine at age 9 months or with a measles and rubella vaccine (second dose) at age 15 months. The primary endpoint, seroprotective response, was defined as a rabbit complement serum bactericidal antibody titre of 8 or higher, with the estimand, given as the difference in the proportions of participants for each of the five meningococcal serogroups who showed this response 28 days after vaccination, assessed in the per-protocol population. The prespecified non-inferiority margin was –10% for all five serogroups in both age groups. The non-inferiority of the NmCV-5 seroprotective response to serogroup X was evaluated in comparison with the lowest seroprotective response for MenACWY-TT among serogroups A, C, W, or Y. Safety was a secondary endpoint, assessed over 6 months in a modified intention-to-treat population that included all participants who received a randomly assigned meningococcal vaccine.
Findings
Between March 24 and Aug 15, 2022, 1325 participants were enrolled and randomly assigned to receive a meningococcal vaccine at either age 9 months (n=602) or age 15 months (n=723). Meningococcal vaccines were administered to 600 of the 602 participants assigned to the 9-month vaccination group during that same period. Between Sept 27, 2022, and Feb 6, 2023, 600 participants received meningococcal vaccines at their 15-month visits. In both groups, 400 participants received NmCV-5 and 200 participants received MenACWY-TT. The per-protocol population assessed in the non-inferiority analysis included 564 participants vaccinated at age 9 months (373 who received NmCV-5 and 191 who received MenACWY-TT) and 549 participants vaccinated at age 15 months (367 who received NmCV-5 and 182 who received MenACWY-TT). Among the participants in the per-protocol population who received NmCV-5 at age 9 months, the difference in seroprotection prevalence for NmCV-5 relative to MenACWY-TT was 0·0% (95% CI –1·0 to 2·0) for serogroup A, –0·5% (–2·3 to 1·9) for serogroup C, –3·0% (–6·3 to 0·8) for serogroup W, and –3·0% (–5·4 to –0·4) for serogroup Y. For serogroup X, non-inferiority was assessed relative to seroprotection for serogroup W in participants who received MenACWY-TT, with a difference of 2·3% (95% CI 0·3 to 4·7). The difference in the prevalence of seroprotection among the participants who received NmCV-5 at age 15 months relative to participants who received MenACWY-TT at age 15 months was 0·8% (95% CI –0·6 to 3·7) for serogroup A, –0·8% (–3·3 to 2·5) for serogroup C, 0·3% (–1·8 to 3·5) for serogroup W, and 1·4% (–0·6 to 4·8) for serogroup Y. For serogroup X, non-inferiority was assessed in relation to seroprotection for serogroup Y in participants who received MenACWY-TT, with a difference of 1·9% (95% CI 0·0 to 4·4). NmCV-5 responses in both age groups were non-inferior to MenACWY-TT responses for all five serogroups. Six serious adverse events were recorded but none were deemed related to vaccination.
Interpretation
When compared with a licensed, quadrivalent meningococcal conjugate vaccine, and given alongside other routine vaccines, a single dose of NmCV-5 was safe and elicited a non-inferior immune response in infants aged 9 months and young children aged 15 months.
CIDRAP article – 5-strain meningitis vaccine shows promise in very young kids (Open access)
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