SynGEM, an intranasal subunit vaccine that introduces the respiratory syncytial virus (RSV), has demonstrated efficacy in actuating lasting immune responses in humans, according to a study published in the American Journal of Respiratory and Critical Care Medicine.
This double-blind, phase 1 randomized placebo-controlled trial (ClinicalTrials.gov Identifier: NCT02958540) included 48 healthy participants between the ages of 18 and 49 years. Participants were randomly assigned to receive either low- or high-dose SynGEM or placebo. The low dose contained 2 mg of bacterium-like particle and 140 μg of F protein and the high dose contained 5 mg of bacterium-like particle and 350 μg of F protein. Both were administered intranasally on a prime-boost schedule. Follow-up to collect nasal and blood lavages continued up to 180 days after administration. Tolerability and safety were primary outcomes in this study, and virus-specific immunogenicity was the secondary objective.
The placebo and vaccinated groups did not differ significantly in terms of physical exams, medical history, or demographic characteristics, and no significant difference was observed between the 2 groups in terms of adverse events. Seropositive participants given SynGEM experienced persistent plasmablast responses and gains in antibodies specific to RSV. High-dose SynGEM was associated with a 1.5-fold plateau response upon the first vaccination that persisted throughout the follow-up period without additional boosting. The low-dose SynGEM achieved plateau responses with a boost at day 28, but the maximum change was 2.4-fold. Those with lower levels of antibodies at baseline showed the strongest response to vaccination. There was heterogeneity in nasal immunoglobulin A responses, although there were no detectable levels of F protein site antibodies at site Ø.
Antibodies competing with palivizumab showed significant increments after prime/boost (prevaccination to day 56, low-dose geometric mean titer, 12.7-13.3; P <.0001; high-dose geometric mean titer, 12.7-13.6; P <.0001).
Limitations to this study included a limited size of antibody responses and a lack of explanation for low serum virus neutralization boosting with the presence of F protein-binding antibodies.
The study researchers concluded that “SynGEM is thus the first non-replicating intranasal RSV subunit vaccine to induce persistent antibody responses in human volunteers.”
Disclosures: This study received support from a Wellcome Trust Translation Award.
Ascough S, Vlachantoni I, Kalyan M, et al. Local and systemic immunity against RSV induced by a novel intranasal vaccine: a randomised, double-blind, placebo-controlled trial [published online February 12, 2019]. Am J Respir Crit Care Med. doi:10.1164/rccm.201810-1921OC