title: Preparation and testing of a Haemophilus influenzae Type b/Hepatitis B surface antigen conjugate vaccine.
abstract: The majority of conjugate vaccines focus on inducing an antibody response to the polysaccharide antigen and the carrier protein is present primarily to induce a T-cell dependent response. In this study conjugates consisting of poly(ribosylribitolphosphate) (PRP) purified from Haemophilus influenzae Type b bound to Hepatitis B virus surface antigen (HBsAg) virus like particles were prepared with the aim of inducing an antibody response to not only the PRP but also the HBsAg. A conjugate consisting of PRP bound to HBsAg via an adipic acid dihydrazide (ADH) spacer induced strong IgG antibodies to both the PRP and HBsAg. When conjugation was performed without the ADH spacer the induction of an anti-PRP response was equivalent to that seen by conjugate with the ADH spacer, however, a negligible anti-HBsAg response was induced. For comparison, PRP was conjugated to diphtheria toxoid (DT) and Vi polysaccharide purified from Salmonella Typhi conjugated to HBsAg both using an ADH spacer. The PRPAH-DT conjugate induced strong anti-PRP and anti-DT responses, the Vi-AHHBsAg conjugate induced a good anti-HBsAg response but not as strong as that induced by the PRPAH-HBsAg conjugate. This study demonstrated that in mice it was possible to induce robust antibody responses to both polysaccharide and carrier protein provided the conjugate has certain physico-chemical properties. A PRPAH-HBsAg conjugate with the capacity to induce anti-PRP and anti-HBsAg responses could be incorporated into a multivalent pediatric vaccine and simplify formulation of such a vaccine.
authors: Vaccine Development Section, International Vaccine Institute, SNU Research Park, 1 Gwanak-ro, Gwanak-gu, Seoul 151-742, Republic of Korea.
authors: So Jung
authors: SJ
authors: An
authors: Vaccine Development Section, International Vaccine Institute, SNU Research Park, 1 Gwanak-ro, Gwanak-gu, Seoul 151-742, Republic of Korea.
authors: Joo Sung
authors: JS
authors: Woo
authors: Vaccine Development Section, International Vaccine Institute, SNU Research Park, 1 Gwanak-ro, Gwanak-gu, Seoul 151-742, Republic of Korea.
authors: Myung Hwa
authors: MH
authors: Chae
authors: Vaccine Development Section, International Vaccine Institute, SNU Research Park, 1 Gwanak-ro, Gwanak-gu, Seoul 151-742, Republic of Korea.
authors: Sudeep
authors: S
authors: Kothari
authors: 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: Rodney
authors: R
authors: Carbis
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D004168:Diphtheria Toxoid / Q000235:genetics / Q000276:immunology; D015721:Diphtheria-Tetanus-Pertussis Vaccine / Q000008:administration & dosage / Q000276:immunology; D018073:Haemophilus Vaccines / Q000276:immunology*; D019741:Haemophilus influenzae type b / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D006514:Hepatitis B Surface Antigens / Q000737:chemistry / Q000235:genetics* / Q000276:immunology*; D017325:Hepatitis B Vaccines / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology; D051379:Mice; D011134:Polysaccharides / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D012485:Salmonella typhi / Q000235:genetics / Q000276:immunology; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000276:immunology*; D058425:Vaccines, Virus-Like Particle / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D004168:Diphtheria Toxoid; D015721:Diphtheria-Tetanus-Pertussis Vaccine; D018073:Haemophilus Vaccines; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D007074:Immunoglobulin G; D011134:Polysaccharides; D018074:Vaccines, Conjugate; D058425:Vaccines, Virus-Like Particle; C008984:polyribitol phosphate
keywords: Conjugate vaccine; Haemophilus influenzae Type b; Hepatitis B; Hepatitis B surface antigen (HBsAg); Polyribosylribitol phosphate (PRP)