A Pentavalent Shigella flexneri LPS-Based Vaccine Candidate Is Safe and Immunogenic in Animal Models

Abstract

A multivalent vaccine is much needed to achieve protection against predominant Shigella serotypes. Recently, we demonstrated the clinical applicability and immunogenic potential of tri-acylated S. flexneri 2a lipopolysaccharide (Ac3-S-LPS). Using a similar approach, we designed a pentavalent LPS candidate vaccine against S. flexneri 1b, 2a, 3a, 6, and Y (PLVF). In this study, we performed molecular and antigenic characterization of the vaccine candidate and its preclinical evaluation. There were no signs of acute toxicity after subcutaneous administration of PLVF in rabbits at a proposed human dose of 125 μg. No pyrogenic reactions and adverse effects associated with chronic toxicity after repeated administration of PLVF were revealed either. The immunization of mice with PLVF led to ≥16-fold increase in S. flexneri 1b-, 2a-, 3a-, 6-, and Y-specific antibodies. In a serum bactericidal antibody (SBA) assay, we registered 54%, 66%, 35%, 60%, and 60% killing of S. flexneri 1b, 2a, 3a, 6, and Y, respectively. In the guinea pig keratoconjunctivitis model, the efficacy was 50% to 75% against challenge with all five S. flexneri serotypes. These studies demonstrate that PLVF is safe, immunogenic over a wide range of doses, and provides protection against challenge with homologous S. flexneri strains, thus confirming the validity of pentavalent design of the combined vaccine.

Shigella Vaccines: The Continuing Unmet Challenge

“…This tri-acylated lipid A variant induces the production of IgG and IgA antibodies with minimal adverse events, positioning it as a prospective candidate for targeting LPS in preventing human shigellosis [105]. Using a similar approach, the same research group designed a pentavalent LPS candidate vaccine targeting S. flexneri 1b, 2a, 3a, 6, and Y (PLVF), which can elicit protective immunity by generating bactericidal antibodies targeting somatic antigen [106]. Other researchers have explored the development and evaluation of needle-free delivery systems for outer membrane vesicles (OMVs) derived from S. flexneri as a pseudo-subunit vaccine [107,108].…”

Vaccine Development against Infectious Diseases: State of the Art, New Insights, and Future Directions

“…Concerning vaccine design and formulations, the development of a pentavalent Shigella flexneri LPS-based vaccine candidate offers hope in the battle against Shigella infections. This study highlights the safety and immunogenicity of this vaccine, marking progress toward a multivalent solution [9]. In this connection, the immune response elicited during an in vitro model of monocyte stimulation with the BCG Moreau Vaccine is presented.…”