title: Preparation and testing of a Vi conjugate vaccine using pneumococcal surface protein A (PspA) from Streptococcus pneumoniae as the carrier protein.
abstract: In the current study pneumococcal surface protein A (PspA) was conjugated to Vi capsular polysaccharide from Salmonella Typhi to make available a vaccine against typhoid fever that has the potential to also provide broad protection from Streptococcus pneumoniae. High yielding production processes were developed for the purification of PspAs from families 1 and 2. The purified PspAs were conjugated to Vi with high recovery of both Vi and PspA. The processes developed especially for PspA family 2 could readily be adapted for large scale production under cGMP conditions. Previously we have shown that conjugation of diphtheria toxoid (DT) to Vi polysaccharide improves the immune response to Vi but can also enhance the response to DT. In this study it was shown that conjugation of PspA to Vi enhanced the anti-PspA response and that PspA was a suitable carrier protein as demonstrated by the characteristics of a T-cell dependent response to the Vi. We propose that a bivalent vaccine consisting of PspA from families 1 and 2 bound to Vi polysaccharide would protect against typhoid fever and has the potential to also protect against pneumococcal disease and should be considered for use in developing countries.
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: Department of Microbiology, University of Alabama at Birmingham, Birmingham AL 35294, USA.
authors.forename: Kristopher R
authors.initials: KR
authors.lastname: Genschmer
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: Jeong Ah
authors.initials: JA
authors.lastname: Kim
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, Birmingham AL 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; D001426:Bacterial Proteins / Q000276:immunology*; D002352:Carrier Proteins / Q000276:immunology*; D005260:Female; D008813:Mice, Inbred ICR; D011008:Pneumococcal Infections / Q000517:prevention & control*; D022242:Pneumococcal Vaccines / Q000276:immunology*; D011135:Polysaccharides, Bacterial / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D012485:Salmonella typhi; D018074:Vaccines, Conjugate / Q000276:immunology
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; D022242:Pneumococcal Vaccines; D011135:Polysaccharides, Bacterial; D011994:Recombinant Proteins; D018074:Vaccines, Conjugate; C051592:pneumococcal surface protein A
keywords: Conjugate vaccine; Pneumococcal surface protein A (PspA); Typhoid fever vaccine; Vaccine development; Vi polysaccharide