Pentavalent meningococcal vaccine shows promise in phase 2 trial

An investigational pentavalent vaccine for Neisseria meningitidis showed promise in a phase 2 trial conducted among toddlers in Mali, researchers reported in The New England Journal of Medicine.

The researchers found that a single dose of the vaccine, NmCV-5, “elicited immune responses that were similar to those observed with two doses of MenACWY-D” — one of the three commercially available quadrivalent meningococcal conjugate vaccines that include serogroups A, C W and Y.

The investigational pentavalent vaccine includes those four serogroups, plus serogroup X, which has increasingly been reported in recent years in Africa’s meningitis belt, according to Milagritos D. Tapia, MD, professor of pediatrics at the University of Maryland’s Center for Vaccine Development, and colleagues.

Tapia and colleagues conducted a phase 2, observer-blinded, randomized, controlled trial involving 375 Malian children aged 12 to 16 months who were assigned in a 2:2:1 ratio to receive either nonadjuvanted NmCV-5 vaccine, alum-adjuvanted NmCV-5, or MenACWY-D in two doses 84 days apart. Study participants visited the trial clinic on days 7, 28, 84, 91, 112 and 168 after the initial baseline visit.

Of the 375 participants, 362 returned for their second dose and 360 completed the trial, Tapia and colleagues reported.

“Solicited local adverse events included tenderness and swelling or induration at the injection site,” they wrote. “Solicited systemic adverse events included irritability, drowsiness, decreased eating, vomiting, and fever.”

A fever with moderate severity was reported once in each of the NmCV-5 groups.

According to the study, at baseline, 15% or less of all trial participants had a serum bactericidal antibody (SBA) titer of at least 128 for all five serotypes.

After 28 days, 97% or more of the participants in both of the NmCV-5 groups had SBA titers of at least 128 against all five serogroups. Comparatively, in the MenACWY-D group, titers of at least 128 were seen in at least 90% of participants but only against serogroups A and W, Tapia and colleagues reported.

At day 84, before administration of the second dose, at least 91% of participants in both of the NmCV-5 groups had SBA titers of at least 128 against all five serogroups. In the MenACWY-D group, more than 90% of participants had titers of at least 128 only for serogroup A.

At day 112, 28 days after the second dose, at least 99% of the participants in both NmCV-5 groups had antibody titers of at least 128 for all five serogroups. Among those in the MenACWY-D group, 91% of participants met the threshold for serogroups A, C, W and Y.

According to the authors, there were no noticeable differences between the adjuvanted and nonadjuvanted NmCV-5 groups for any serogroup at any point in time throughout the trial.

“The results of this trial suggest that NmCV-5 has the potential to affect outbreaks of serotype A, C, W, Y, or X in the sub-Saharan African meningitis belt, a finding that is analogous to the success seen with MenAfriVac,” the authors wrote. “Several studies have shown that expanding the coverage of a monovalent serogroup A to a multivalent vaccine would be cost-effective.”