By Tara Haelle
FROM THE PEDIATRIC INFECTIOUS DISEASE JOURNAL
A booster shot of the investigational combined meningococcal vaccine MenABCWY provided robust antibody response against five serogroups of meningococcal disease, according to results of a phase 2, randomized, controlled trial.
“The use of MenABCWY as a two-dose primary vaccination in children 11-12 years of age followed by a booster dose administered 12 months later to replace separate administration of quadrivalent MenACWY and serogroup B vaccines would have the benefit of providing protection against all five clinically relevant meningococcal serogroups at an earlier age than that afforded by current recommendations,” wrote Leszek Szenborn, MD, of Wroclaw Medical University in Poland, and his associates.
“The further clinical development of a combination pentavalent MenABCWY vaccine is warranted, in view of its potential to simplify vaccine regimens and improve meningococcal vaccination coverage,” they wrote in the Pediatric Infectious Disease Journal.
Up to 1 in 10 people die after developing meningococcal disease from the bacteria Neisseria meningitidis, and serogroups A, B, C, W, X, and Y are responsible for nearly all cases of invasive meningococcal disease. Serogroup B, and increasingly serogroup W, cause most cases in Europe while serogroups B, C, and Y cause most U.S. cases, Dr. Szenborn and his associates said.
Their previous phase 2 study showed the noninferiority of a two-dose primary series of two MenABCWY vaccine formulations (one at a quarter the dose of the other), compared with a single dose of the MenACWY-CRM vaccine. The participants, all aged 10-25 years, also showed a strong immune response against serogroup B strains.
This study enrolled 194 of the original 419 participants in the previous study. They were randomized to receive either a placebo or a MenABCWY booster 24 months after their primary series:
51 participants initially vaccinated with MenABCWY received a MenABCWY booster or placebo.
41 participants initially vaccinated with MenABCWY at one-quarter dose received either a quarter-dose MenABCWY booster or placebo.
43 participants initially vaccinated with 4CMenB (Bexsero, GlaxoSmithKline) received a MenABCWY booster or a quarter-dose MenABCWY booster.
59 participants initially vaccinated with MenACWY-CRM (Menveo, GlaxoSmithKline) received a MenABCWY booster, a quarter-dose MenABCWY booster, or a placebo.
The primary outcome was the seroresponse to all five serogroups, measured with bactericidal assay with human complement (hSBA) titers at 1 month and 12 months after the booster; 190 participants completed the study.
For serogroups A, C, W, and Y, seroresponse at 1 month referred to the percentage of participants with at least a fourfold increase in hSBA titers from a baseline of at least fourfold titers, or at least eightfold hSBA titers in those with a baseline below fourfold. The 12-month seroresponse required eightfold hSBA titers.
For serogroup B, seroresponse required at least fivefold hSBA titers for both 1 and 12 months.
One month after the booster, seroresponse against A, C, W, and Y serogroups ranged from 73% to 100%, depending on participants’ primary series. Those with the MenABCWY primary series had a seroresponse range of 85%-96% (depending on serogroup) 1 month after the booster. Seroresponse ranged from 73% to 100% in those with a 4CMenB primary series and from 83% to 95% in those with a MenACWY-CRM primary series.
One year after the booster, at least 67% of the participants met the seroresponse threshold for serogroups A, C, W, and Y, regardless of primary series vaccine, with one exception. Only 45% of participants who received the 4CMenB primary series met the threshold for serogroup Y.
“The rate of persistence [of immune response] against serogroup B strains at 1 year post booster in the 4CMenB/ABCWY group was 45%-100%, and in the ACWY/ ABCWY group was 14%-29%,” Dr. Szenborn and his associates said.
The most common adverse events following booster vaccination was pain at the injection site, headache, and fatigue. No serious adverse events or deaths occurred during the study or after the booster. Incidence of adverse events in this study was similar to the incidence for MenABCWY, MenACWY-CRM, and 4CMenB vaccines in the previous study.
The study’s limitations include small sample sizes in each of the primary series vaccine groups and limited generalizability of the findings. The authors recommended that future studies include a control group who received a primary series with MenACWY, “because such a comparison would provide important data on the protection afforded against serogroup B in adolescents younger than 16-19 years, the age at which immunization is currently recommended.”
The research was funded by Novartis Vaccines and Diagnostics, which is now part of the GlaxoSmithKline group of companies. Dr. Szenborn received personal fees from Novartis and GlaxoSmithKline during this study. Dr. Diego D’Agostino and Dr. Daniela Toneatto are GlaxoSmithKline employees, and Dr. Jo Anne Welsch was a GlaxoSmithKline employee at the time of the study. Dr. Igor Smolenov was a Novartis employee at the time of the study, and Dr. Stan L. Block is a grant investigator and received a research grant from Novartis. The other investigators had no conflicts of interest.
SOURCE: Szenborn L et al. Pediatr Infect Dis J. 2018;37:475-82.
This micrograph depicts the presence of aerobic Gram-negative Neisseria meningitidis diplococcal bacteria.