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Enhanced safety and immunogenicity of a pneumococcal surface antigen A mutant whole‐cell inactivated pneumococcal vaccine
Author(s) -
David Shan C,
Laan Zoe,
Minhas Vikrant,
Chen Austen Y,
Davies Justin,
Hirst Timothy R,
McColl Shaun R,
Alsharifi Mohammed,
Paton James C
Publication year - 2019
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1111/imcb.12257
Subject(s) - immunogenicity , serotype , virology , microbiology and biotechnology , vaccination , streptococcus pneumoniae , antigen , pneumococcal conjugate vaccine , biology , immunology , antibiotics
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 T H 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.