New pentavalent vaccine promising for eliminating meningitis across Africa: NEJM

The new vaccine against meningococcal disease, a cause of blood poisoning and meningitis, was shown to be safe and induces a robust immune response across five strains of meningococcal bacteria: A, C, W, Y and X. The findings appeared in The New England Journal of Medicine (NEJM) on May 25, 2023.

A previous phase 2 trial showed that a single dose of NmCV-5 vaccine-elicited immune responses similar to those of MenACWY-D's two doses. The new trial showed the investigational vaccine-elicited immune responses to the four serotypes of the MenACWY-D vaccine and serogroup X, recently reported in Africa's meningitis belt. MenACWY-D is one of the three commercially available quadrivalent meningococcal conjugate vaccines.

There is a need for an effective, affordable, multivalent meningococcal conjugate vaccine to prevent epidemic meningitis in the African meningitis belt. Also, there is limited data on the immunogenicity and safety of NmCV-5, a pentavalent vaccine which targets the X, Y, W, C, and A serogroups. To fill this knowledge gap, Ed Clarke, Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, Banjul, Gambia, and associates conducted a phase 3, noninferiority trial involving healthy 2-to-29-year-olds in Mali and Gambia.

One thousand eight hundred participants were randomly assigned in a ratio of 2:1 to receive a single intramuscular dose of NmCV-5 or the quadrivalent vaccine MenACWY-D. An immunogenicity assessment was done on day 28.

Based on the difference in the percentage of participants with seroresponse or geometric mean titer (GMT) ratios, the researchers assessed the noninferiority of NmCV-5 to MenACWY-D. A comparison was made between serogroup X responses in the NmCV-5 group and the lowest response among the MenACWY-D serogroups. A safety assessment was also done.

The study revealed the following findings:

• In the NmCV-5 group, the percentage of participants with a seroresponse ranged from 70.5% for serogroup A to 98.5% for serogroup W; the percentage with a serogroup X response was 97.2%.
• The overall difference between the two vaccines in seroresponse for the four shared serogroups ranged from 1.2 percentage points for serogroup W to 20.5 percentage points for serogroup A.
• The overall GMT ratios for the four shared serogroups ranged from 1.7 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).

"For all four serotypes in common with the MenACWY-D vaccine, the NmCV-5 vaccine-elicited immune responses noninferior to those elicited by the MenACWY-D vaccine," the researchers wrote. "NmCV-5 also elicited immune responses to serogroup X. No safety concerns were evident."

Reference:

Haidara et al, Meningococcal ACWYX Conjugate Vaccine in 2-to-29-Year-Olds in Mali and Gambia. New England Journal of Medicine. DOI: 10.1056/NEJMoa2214924