Chen WH, et al. - Researchers conducted a first-in-man, phase 1 study assessing the NmCV-5 pentavalent meningococcal conjugate vaccine targeting A, C, Y, W, and X serogroups. Participants were able to tolerate the adjuvanted and non-adjuvanted NmCV-5 vaccines and did not suffer concerning adverse effects. The vaccines resulted in immune responses that are predicted to confer protection against all five targeted serogroups of invasive meningococcal disease.

Methods

• At a research clinic in Baltimore (MD, US), a single-center, double-blind, randomized controlled trial was performed.
• Healthy adults aged 18–45 years with no history of meningococcal vaccination or previous meningococcal infection were eligible.
• By an SAS-generated random schedule, participants (1:1:1) were randomly assigned to a single, 0.5 mL, intramuscular injection of aluminum-phosphate adjuvanted NmCV-5, non-adjuvanted NmCV-5, or control (the quadrivalent meningococcal conjugate vaccine Menactra).
• A permuted block design with randomly chosen block sizes of three and six was used in the randomization sequence.
• Participants and study personnel remained masked to treatment.
• Participants were observed for adverse reactions in the clinic for 60 minutes after vaccination.
• Temperature and injection site or systemic reactions were recorded daily by the participants at home; participants returned to the clinic for follow-up visits on days 7, 28, and 84 for safety assessments; blood samples were also collected on day 7 for safety laboratory assessment.
• Researchers collected serum before vaccination and 28 days after vaccination for immunological assessment with a rabbit complement-dependent serum bactericidal antibody (rSBA) assay.
• Primarily, they performed an intention-to-treat assessment of safety, measured local and systemic reactogenicity over 7 days, unsolicited adverse events through 28 days, and serious adverse events over 6 months.
• Secondarily, they assessed immunogenicity via a per-protocol analysis of rSBA before and 28 days after vaccination.

Results

• Twenty participants were assigned to each vaccine between August 17, 2016 and February 16, 2017.
• Participants tolerated all vaccines.
• The most common local reaction was pain; it occurred in 12 (60%), ten (50%), and seven (35%) participants in the adjuvanted NmCV-5, non-adjuvanted NmCV-5, and control groups, respectively.
• Headache was the most common systemic reaction, occurring in five (25%), three (15%), and three (15%), respectively.
• Most solicited reactogenicity adverse reactions in this trial were mild (60 [74%] of 81) and self-limiting.
• The three vaccination groups had no significant differences in proportions of individuals with each solicited reaction (p > 0.300 for all comparisons).
• Researchers identified no serious adverse events; 19 unsolicited non-serious adverse events were encountered in 14 (23%) participants.
• High rSBA titers against all five meningococcal serogroups were elicited by both adjuvanted and non-adjuvanted NmCV-5.
• In this study, they noted the pre-vaccination geometric mean titers (GMTs) ranging from 3.36 to 53.80 for the control, from 6.28 to 187.00 for the adjuvanted vaccine, and from 4.29 to 350.00 for the non-adjuvanted vaccine, and the post-vaccination GMT ranging from 3.14 to 3,214 for the control, from 1,351 to 8,192 for the adjuvanted vaccine, and from 1607 to 11,191 for the non-adjuvanted vaccine.
• For the adjuvanted and non-adjuvanted NmCV-5, predicted seroprotective responses (ie, an increase in rSBA titers of eight times or more) were like control responses for all five serogroups.