Assessments of the safety and immunogenicity of a novel hexavalent (Ia, Ib, II, III, IV, and V) conjugate vaccine (GBS6) against group B streptococcus (GBS) in adults was found to be well tolerated and elicited robust immune responses, according to data published in The Lancet Infectious Diseases. Investigators support the further evaluation of GBS6 in pregnant women.
GBS is a major cause of invasive disease in young infants. Infants born to mothers with sufficient pre-existing anti-GBS capsular IgG antibodies are at reduced risk. Maternal vaccination may be a potential prevention strategy. A phase 1/2 placebo-controlled, observer-blinded, dose-escalation trial was conducted at four clinical research centers in the United States (ClinicalTrials.gov, NCT03170609).
Healthy non-pregnant adults aged 18 to 49 years were randomly assigned to low-, medium-, or high-dose groups. Participants in sentinel cohorts were randomly assigned 2:2:1, and expanded cohort participants were randomly assigned 4:4:1 to receive GBS6 with aluminum phosphate (AlPO4), GBS6 without AlPO4, or placebo (saline control). A single 0.5 mL dose of either saline placebo or 5, 10, or 20 μg capsular polysaccharide per serotype in the low-, medium-, and high-dose groups, respectively, were administered by intramuscular injection into the deltoid muscle on day 1.
Of 365 total participants, 364 (n=52 participants in each dose group) were vaccinated and included in the safety analysis. Unsolicited adverse events were reported in 29% (n=15) of participants in the 5 μg with AlPO4 group, 25% (n=13) in the 5 μg without AlPO4 group, 42% (n=22) in the 10 μg with AlPO4 group, 23% (n=12) in the 10 μg without AlPO4 group, 48% (n=25) in the 20 μg with AlPO4 group, 40% (n=21) in the 20 μg without AlPO4 group, and 38% (n=20) in the placebo group.
The most common of these events were infections and infestations in any dose or formulation of GBS6, ranging from 12% (n=6) in the 10 μg without AlPO4 group to 29% (n=15) in the 20 μg with AlPO4 group and placebo group. One serious adverse event was reported in 5 μg GBS6 with AlPO4 group, 10 μg GBS6 with AlPO4 group, and 20 μg GBS6 with AlPO4 group, none of which were considered related to the vaccine. Investigators also report 11 of the 365 participants were excluded from the evaluable immunogenicity population. This included one participant who didn’t receive the vaccine, and 10 who were withdrawn for various reasons 1 month post vaccination.
GBS serotype-specific IgG geometric mean concentrations in all groups increased rapidly from baseline to 1 week after vaccination, peaked at 2 weeks, stabilized by 1 month, and then declined gradually but remained higher than placebo at 6 months. The generalizability of these results may be limited due to the study being performed in the United States among a homogeneous non-pregnant population.
Further clinical assessment of the vaccine is underway in another geographic region in a study of pregnant women (ClinicalTrials.gov, NCT03765073). Investigators believe data from this work will provide the opportunity to assess GBS6 in diverse populations.
Results from this first-in-human trial do show “GBS6 was safe, tolerable, and elicited an immune response among healthy, non-pregnant adults at all doses and formulations tested.” Investigators conclude that this trial supports further evaluation of the vaccine in pregnant women and the amount of passive antibody transfer in newborn babies.
Disclosure: The study was funded by Pfizer. Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Absalon J, Segall N, Block SL, et al. Safety and immunogenicity of a novel hexavalent group B streptococcus conjugate vaccine in healthy, non-pregnant adults: a phase 1/2, randomised, placebo-controlled, observer-blinded, dose-escalation trial. Published online September 3, 2020. Lancet Infect Dis. doi:10.1016/S1473-3099(20)30478-3