title: 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.
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.
authors.affiliation: Vaccine Development Section, International Vaccine Institute, SNU Research Park, 1 Gwanak-ro, Gwanak-gu, Seoul, 151-742, Republic of Korea; School of Pharmacy, Sungkyunkwan University, 300 Chunchun-dong, Suwon 440-746, Republic of Korea.
authors.forename: Neha
authors.initials: N
authors.lastname: Kothari
authors.affiliation: Vaccine Development Section, International Vaccine Institute, SNU Research Park, 1 Gwanak-ro, Gwanak-gu, Seoul, 151-742, Republic of Korea.
authors.forename: Sudeep
authors.initials: S
authors.lastname: Kothari
authors.affiliation: Vaccine Development Section, International Vaccine Institute, SNU Research Park, 1 Gwanak-ro, Gwanak-gu, Seoul, 151-742, Republic of Korea.
authors.forename: Young Joo
authors.initials: YJ
authors.lastname: Choi
authors.affiliation: Vaccine Development Section, International Vaccine Institute, SNU Research Park, 1 Gwanak-ro, Gwanak-gu, Seoul, 151-742, Republic of Korea.
authors.forename: Ayan
authors.initials: A
authors.lastname: Dey
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, Alabama 35294, USA.
authors.forename: David E
authors.initials: DE
authors.lastname: Briles
authors.affiliation: School of Pharmacy, Sungkyunkwan University, 300 Chunchun-dong, Suwon 440-746, Republic of Korea.
authors.forename: Dong Kwon
authors.initials: DK
authors.lastname: Rhee
authors.affiliation: Vaccine Development Section, International Vaccine Institute, SNU Research Park, 1 Gwanak-ro, Gwanak-gu, Seoul, 151-742, Republic of Korea. Electronic address: rcarbis@ivi.int.
authors.forename: Rodney
authors.initials: R
authors.lastname: Carbis
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis / Q000097:blood*; D001426:Bacterial Proteins / Q000737:chemistry / Q000145:classification / Q000276:immunology*; D056738:Cross Protection; D003429:Cross Reactions; D005260:Female; D018796:Immunoconjugates / Q000737:chemistry / Q000276:immunology; D017578:Immunoglobulin Class Switching; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood; D051379:Mice; D008813:Mice, Inbred ICR; D011008:Pneumococcal Infections / Q000097:blood / Q000276:immunology / Q000401:mortality / Q000517:prevention & control*; D022242:Pneumococcal Vaccines / Q000008:administration & dosage / Q000138:chemical synthesis / Q000276:immunology*; D011135:Polysaccharides, Bacterial / Q000737:chemistry / Q000276:immunology*; D012485:Salmonella typhi / Q000187:drug effects / Q000276:immunology; D013296:Streptococcus pneumoniae / Q000187:drug effects / Q000276:immunology; D016019:Survival Analysis; D058408:Th1-Th2 Balance; D014435:Typhoid Fever / Q000097:blood / Q000276:immunology / Q000401:mortality / Q000517:prevention & control*; D014436:Typhoid-Paratyphoid Vaccines / Q000008:administration & dosage / Q000138:chemical synthesis / Q000276:immunology*; D018074:Vaccines, Conjugate
chemical_list: D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D018796:Immunoconjugates; D007074:Immunoglobulin G; D022242:Pneumococcal Vaccines; D011135:Polysaccharides, Bacterial; D014436:Typhoid-Paratyphoid Vaccines; D018074:Vaccines, Conjugate; C054154:capsular polysaccharide, Salmonella; C051592:pneumococcal surface protein A
keywords: Salmonella Typhi; Streptococcus pneumoniae; Vaccine development; Vi-PspA conjugate vaccine