A bivalent conjugate vaccine containing PspA families 1 and 2 has the potential to protect against a wide range of Streptococcus pneumoniae strains and Salmonella Typhi

• Published in: Vaccine 2015-02, Vol.33 (6), p.783-788
• Main Authors: Kothari, Neha, Kothari, Sudeep, Choi, Young Joo, Dey, Ayan, Briles, David E, Rhee, Dong Kwon, Carbis, Rodney
• Format: Article
• Language: English
• Subjects: Allergy and Immunology; Animals; Antibodies, Bacterial - biosynthesis; Antibodies, Bacterial - blood; Antigens; Bacteria; Bacterial Proteins - chemistry; Bacterial Proteins - classification; Bacterial Proteins - immunology; Binding sites; Cross Protection; Cross Reactions; Cytokines; Female; Gram-positive bacteria; Immune response; Immunoconjugates - chemistry; Immunoconjugates - immunology; Immunoglobulin Class Switching; Immunoglobulin G - biosynthesis; Immunoglobulin G - blood; Mice; Mice, Inbred ICR; Pneumococcal Infections - blood; Pneumococcal Infections - immunology; Pneumococcal Infections - mortality; Pneumococcal Infections - prevention & control; Pneumococcal Vaccines - administration & dosage; Pneumococcal Vaccines - chemical synthesis; Pneumococcal Vaccines - immunology; Polysaccharides, Bacterial - chemistry; Polysaccharides, Bacterial - immunology; Proteins; Salmonella Typhi; Salmonella typhi - drug effects; Salmonella typhi - immunology; Streptococcus infections; Streptococcus pneumoniae; Streptococcus pneumoniae - drug effects; Streptococcus pneumoniae - immunology; Survival Analysis; Th1-Th2 Balance; Typhoid Fever - blood; Typhoid Fever - immunology; Typhoid Fever - mortality; Typhoid Fever - prevention & control; Typhoid-Paratyphoid Vaccines - administration & dosage; Typhoid-Paratyphoid Vaccines - chemical synthesis; Typhoid-Paratyphoid Vaccines - immunology; Vaccine development; Vaccines; Vaccines, Conjugate; Vi-PspA conjugate vaccine
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2014.12.032

Abstract Previously we showed that conjugation of pneumococcal surface protein A (PspA) to Vi capsular polysaccharide from Salmonella Typhi enhanced the anti-PspA response without the need to add adjuvant. In the current study conjugates consisting of the α helical regions of PspA families 1 or 2 bound to Vi were used to vaccinate mice to test their ability to protect against a lethal intravenous challenge of a range of various strains of Streptococcus pneumoniae . Conjugate vaccine containing PspA family 1 provided good protection from PspA family 1 challenge strains but offered very little protection against PspA family 2 challenge strains. Similarly, PspA family 2 conjugates provided good protection from PspA family 2 challenge strains and poor protection against PspA family 1 challenge strains. This observation was supported by the low levels of cross-reactivity of PspA antibodies seen in ELISA plates coated with the heterologous PspA family. Cytokine profiles showed a mixed Th1/Th2 response to Vi and the Vi-PspA conjugates. IgG subclass analysis of the anti-Vi response showed a shift from predominantly IgG2a/3 to IgG1 after conjugation to PspA was consistent with other polysaccharide conjugate vaccines. The results demonstrate that conjugation of the α helical region of PspA to Vi enhances its capacity to induce a protective immune response and that a vaccine based on the α helical region of PspA should contain PspA from both families 1 and 2 to achieve broad cross-protection.