Immunization of Rabbits with a Quadrivalent Bioconjugate Vaccine Induces Functional Antibodies Reactive with Isolates from Kenya

Diarrheal diseases are a leading cause of global morbidity and mortality, disproportionately affecting children in resource-limited settings. Although improvements in hygiene and access to clean water are helpful, vaccines are considered essential due to the low infectious dose of species and increasing antibiotic resistance. Building on achievements with conjugate vaccines, a safe and immunogenic novel bioconjugate vaccine linking O-antigen to Pseudomonas aeruginosa exoprotein A has been developed to induce immunity against Shigella flexneri 2a, 3a, and 6 and S. sonnei. This study evaluated the breadth of reactivity and functionality of pooled serum from rabbits immunized with monovalent and quadrivalent bioconjugates formulated with or without an adjuvant against serotypes isolated in Kenya. Rabbit sera were assayed by colony blot for reactivity with 67 isolates of serotypes targeted by the vaccine, S. flexneri (2a, 3a, and 6) and S. sonnei, and 42 isolates of serotypes not targeted by the vaccine, S. flexneri (1b, 2b, 4a, and 4b), S. boydii, and S. dysenteriae. isolates testing positive in the colony blot assay were then used to assess functional activity using a bactericidal assay. Of the 41 isolates targeted by the vaccine, 22 were reactive with the adjuvanted quadrivalent and the respective monovalent rabbit sera. The S. flexneri 2a and 3a monovalent rabbit serum cross-reacted with S. flexneri 3a, 2b, and 2a, respectively. Immunization with the adjuvanted quadrivalent vaccine also induced cross-reactivity with isolates of S. flexneri 2b, 4a, and 4b. Collectively, these results suggest that the quadrivalent vaccine may be more broadly protective than designed, offering a promising solution to infections. Diarrheal diseases are the third leading cause of death globally, disproportionally affecting low- to middle-income countries like Kenya, with species being the leading cause of bacterial diarrhea, especially in children. The low infectious dose and high antibiotic resistance levels complicate treatment, leading to long-term sequelae that necessitate control measures such as vaccines to reduce morbidity and mortality rates, especially among children under 5 years of age. A quadrivalent bioconjugate vaccine was recently developed to safely and effectively induce immunity against four important spp. This study demonstrates the breadth of reactivity and functionality of the parenterally administered bioconjugate vaccine by evaluating the ability of rabbit sera to bind and kill isolates recently collected in Kenya. These results suggest that the quadrivalent vaccine may be more broadly protective than designed and may offer a promising solution to the morbidity and mortality associated with infections.