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Type: Journal article
Title: Enhanced safety and immunogenicity of a pneumococcal surface antigen A mutant whole-cell inactivated pneumococcal vaccine
Author: David, S.C.
Laan, Z.
Minhas, V.
Chen, A.Y.
Davies, J.
Hirst, T.R.
McColl, S.R.
Alsharifi, M.
Paton, J.C.
Citation: Immunology and Cell Biology, 2019; 97(8):1-14
Publisher: Wiley Online Library
Issue Date: 2019
ISSN: 0818-9641
Statement of
Shannon C David, Zoe Laan, Vikrant Minhas, Austen Y Chen, Justin Davies, Timothy R Hirst, Shaun R McColl, Mohammed Alsharifi, James C Paton
Abstract: Existing capsular polysaccharide-based vaccines against pneumococcal disease are highly effective against vaccine-included serotypes, but they are unable to combat serotype replacement. We have developed a novel pneumococcal vaccine that confers serotype-independent protection, and could therefore constitute a "universal" vaccine formulation. This preparation is comprised of whole un-encapsulated pneumococci inactivated with gamma irradiation (γ-PN), and we have previously reported induction of cross-reactive immunity after nonadjuvanted intranasal vaccination. To further enhance vaccine immunogenicity and safety, we modified the pneumococcal vaccine strain to induce a stressed state during growth. Specifically, the substrate binding component of the psaBCA operon for manganese import was mutated to create a pneumococcal surface antigen A (psaA) defective vaccine strain. psaA mutation severely attenuated the growth of the vaccine strain in vitro without negatively affecting pneumococcal morphology, thereby enhancing vaccine safety. In addition, antibodies raised against vaccine preparations based on the modified strain [γ-PN(ΔPsaA)] showed more diversified reactivity to wild-type pneumococcal challenge strains compared to those induced by the original formulation. The modified vaccine also induced comparable protective TH 17 responses in the lung, and conferred greater protection against lethal heterologous pneumococcal challenge. Overall, the current study demonstrates successful refinement of a serotype-independent pneumococcal vaccine candidate to enhance safety and immunogenicity.
Keywords: gamma-irradiation
mucosal immunity
pneumococcal vaccine
Rights: © 2019 Australian and New Zealand Society for Immunology Inc.
DOI: 10.1111/imcb.12257
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