Researchers are optimistic about a more affordable multivalent meningococcal vaccine becoming a future option after a randomised trial in the African meningitis belt showed the investigational jab proved safe and with non-inferior immunogenicity to a licensed quadrivalent product.
The phase III study included candidates aged two to 29 in Mali and The Gambia – the target demographic in outbreak-response campaigns – and the pentavalent vaccine (NmCV-5) elicited similar seroresponse rates across shared serogroups along with favourable geometric mean titer (GMT) ratios versus the licensed vaccine, MenACWY-D (Menactra), according to Ed Clarke, MBChB, of the London School of Hygiene and Tropical Medicine in Banjul, Gambia, and colleagues.
On the basis of both seroresponse and GMT ratios against serogroups A, C, W, Y, and X, non-inferiority was demonstrated in all three age subgroups: two to 10, 11 to 17, and 18 to 29, reports MedPage Today.
The trial’s findings are expected to support the licensure and prequalification of NmCV-5 by the World Health Organisation (WHO) as the first vaccine to target the emerging serogroup X, the researchers wrote in the New England Journal of Medicine.
For seroresponse measured at 28 days, the overall difference with NmCV-5 versus MenACWY-D, respectively, ranged from 1.2 percentage points (96% CI -0.3 to 3.1) for serogroup W to 20.5 percentage points (96% CI 15.4-25.6) for serogroup A, and the pentavalent vaccine also elicited a strong immune response for serogroup X:
Serogroup A: 70.5% vs 50.0%
Serogroup C: 97.9% vs 95.5%
Serogroup W: 98.5% vs 97.4%
Serogroup Y: 97.0% vs 92.0%
Serogroup X: 97.2% vs 9.5%
GMT ratios favoured the NmCV-5 vaccine across all serogroups of Neisseria meningitidis, the predominant cause of meningitis epidemics, ranging from 1.7 (95% CI 1.5-1.9) for serogroup A to 2.8 (95% CI 2.3-3.5) for serogroup C, with serogroup X responses also hitting prespecified criteria for noninferiority for both measures.
“On the basis of these trial data, NmCV-5 may emerge as a tool to support meningococcal disease control, particularly across the meningitis belt of sub-Saharan Africa, and contribute to epidemic elimination and the other goals of the global road map for the Defeating Meningitis by 2030 programme,” said Clarke and colleagues.
An estimated 2.5m cases of meningitis were reported worldwide in 2019, resulting in more than 236 000 deaths and long-term neurologic disabilities or other complications for many who survive invasive disease.
The highest burden is seen in the African meningitis belt, a stretch of sub-Saharan Africa spanning from The Gambia and Senegal to Ethiopia.
“Meningitis is a deadly disease with the ability to spread like wildfire during an outbreak, and this affects all ages, most especially within the meningitis belt region,” said co-author Ama Umesi, MBBS, also of the London School of Hygiene and Tropical Medicine in Banjul.
While MenACWY-D and three other quadrivalent meningococcal conjugate vaccines targeting serogroups A, C, W, and Y have been licensed and prequalified by the WHO, supply and cost-constraints have limited their use, the researchers said.
“The technology used in the production of the NmCV-5 vaccine is based on cost-effective methods for carrier protein production, polysaccharide fermentation and purification, and chemical conjugation,” they noted. “Thus, the vaccine is expected to be made available at a cost lower than that of the existing quadrivalent vaccines.”
Of the six serogroups of meningococcus that can cause invasive disease (A, B, C, W, X and Y), serogroup A had historically been the leading cause of disease in the meningitis belt, until mass vaccinations with MenAfriVac – led by PATH, the WHO, and others – virtually eliminated cases caused by this serogroup, noted Dr David Stephens of Emory University in Atlanta.
“A powerful feature contributing to the remarkable effectiveness of the MenAfriVac vaccine and other bacterial meningitis conjugate vaccines introduced in large-scale campaigns is the reduction of human-to-human respiratory transmission of encapsulated N. meningitidis and the induction of herd protection among unvaccinated persons,” he wrote in an accompanying editorial. “The effects on transmission can persist for decades.”
“With the development of new, affordable vaccines such as NmCV-5, we are a step closer to worldwide control of meningococcal disease and the burden of meningitis.”
Study details
Meningococcal ACWYX Conjugate Vaccine in 2-to-29-Year-Olds in Mali and Gambia
Fadima Haidara, Ama Umesi, Samba Sow, Magnus Ochoge, Fatoumata Diallo, Abdulazeez Imam, Youssouf Traore, Lucy Affleck, Moussa Doumbia, Bubacarr Daffeh, Mamoudou Kodio, Oghenebrume Wariri, et al.
Published in the New England Journal of Medicine on 25 May 2023-05-25
Abstract
Background
An effective, affordable, multivalent meningococcal conjugate vaccine is needed to prevent epidemic meningitis in the African meningitis belt. Data on the safety and immunogenicity of NmCV-5, a pentavalent vaccine targeting the A, C, W, Y, and X serogroups, have been limited.
Methods
We conducted a phase 3, noninferiority trial involving healthy 2-to-29-year-olds in Mali and Gambia. Participants were randomly assigned in a 2:1 ratio to receive a single intramuscular dose of NmCV-5 or the quadrivalent vaccine MenACWY-D. Immunogenicity was assessed at day 28. The noninferiority of NmCV-5 to MenACWY-D was assessed on the basis of the difference in the percentage of participants with a seroresponse (defined as prespecified changes in titer; margin, lower limit of the 96% confidence interval [CI] above −10 percentage points) or geometric mean titer (GMT) ratios (margin, lower limit of the 98.98% CI >0.5). Serogroup X responses in the NmCV-5 group were compared with the lowest response among the MenACWY-D serogroups. Safety was also assessed.
Results
A total of 1800 participants received NmCV-5 or MenACWY-D. In the NmCV-5 group, the percentage of participants with a seroresponse ranged from 70.5% (95% CI, 67.8 to 73.2) for serogroup A to 98.5% (95% CI, 97.6 to 99.2) for serogroup W; the percentage with a serogroup X response was 97.2% (95% CI, 96.0 to 98.1). The overall difference between the two vaccines in seroresponse for the four shared serogroups ranged from 1.2 percentage points (96% CI, −0.3 to 3.1) for serogroup W to 20.5 percentage points (96% CI, 15.4 to 25.6) for serogroup A. The overall GMT ratios for the four shared serogroups ranged from 1.7 (98.98% CI, 1.5 to 1.9) for serogroup A to 2.8 (98.98% CI, 2.3 to 3.5) for serogroup C. The serogroup X component of the NmCV-5 vaccine generated seroresponses and GMTs that met the prespecified noninferiority criteria. The incidence of systemic adverse events was similar in the two groups (11.1% in the NmCV-5 group and 9.2% in the MenACWY-D group).
Conclusions
For all four serotypes in common with the MenACWY-D vaccine, the NmCV-5 vaccine elicited immune responses that were noninferior to those elicited by the MenACWY-D vaccine. NmCV-5 also elicited immune responses to serogroup X. No safety concerns were evident.
NEJM accompanying editorial – Global Control of Meningococcal Disease (Open access)
MedPage Today article – Pentavalent Vaccine Candidate for Meningitis Makes Its Case (Open access)
See more from MedicalBrief archives:
Multi-billion rand strategy from WHO to eradicate Africa’s meningitis by 2030
Trial to tackle HIV-associated cryptococcal meningitis deaths in Africa
A silent crisis: Hearing outcomes in children with meningitis
Afro-European project: SA study for treatment of cryptococcal meningitis