title: Safety and immunogenicity of a combined hepatitis B virus-Haemophilus influenzae type B vaccine comprising a synthetic antigen in healthy adults.
abstract: The combined HB-Hib vaccine candidate Hebervac HB-Hib (CIGB, La Habana), comprising recombinant HBsAg and tetanus toxoid conjugate synthetic PRP antigens has shown to be highly immunogenic in animal models. A phase I open, controlled, randomized clinical trial was carried out to assess the safety and immunogenicity profile of this bivalent vaccine in 25 healthy adults who were positive for antibody to HBsAg (anti-HBs). The trial was performed according to Good Clinical Practices and Guidelines. Volunteers were randomly allocated to receive the combined vaccine or simultaneous administration of HB vaccine Heberbiovac-HB and Hib vaccine QuimiHib (CIGB, La Habana). All individuals were intramuscularly immunized with a unique dose of 10 microg HBsAg plus 10 microg conjugated synthetic PRP. Adverse events were actively recorded after vaccine administration. Total anti-HBs and IgG anti-PRP antibody titers were evaluated using commercial ELISA kits at baseline and 30 days post-vaccination. The combined vaccine candidate was safe and well tolerated. The most common adverse reactions were local pain, febricula, fever and local erythema. These reactions were all mild in intensity and resolved without medical treatment. Adverse events were mostly reported during the first 6-72 hours post-vaccination. There were no serious adverse events during the study. No severe or unexpected events were either recorded during the trial. The combined vaccine elicited an anti-HBs and anti-PRP booster response in 100% of subjects at day 30 of the immunization schedule. Anti-HBs and anti-PRP antibody levels had at least a two-fold increase compared to baseline sera. Even more, anti-HBs antibody titer showed a four-fold increase in 100% of volunteers in the study group. The results indicate that the combined HB-Hib vaccine produces increased antibody levels in healthy adults who have previously been exposed to these two antigens. To our knowledge, this is the first demonstration of safety and immunogenicity for a combined vaccine comprising recombinant HBV and synthetic Hib antigens. The present results support phase I-II clinical trial in the target population, two months old healthy infants.
authors.affiliation: Vaccine Division, Vaccine Clinical Trials Deptartment, Center for Genetic Engineering and Biotechnology, Cubanacán, Playa, Habana City, Cuba. aristides.aguilar@cigb.edu.cu <aristides.aguilar@cigb.edu.cu>
authors.forename: Arístides
authors.initials: A
authors.lastname: Aguilar-Betancourt
authors.forename: Carlos Alberto
authors.initials: CA
authors.lastname: González-Delgado
authors.forename: Z
authors.initials: Z
authors.lastname: Cinza-Estévez
authors.forename: Jesus
authors.initials: J
authors.lastname: Martínez-Cabrera
authors.forename: Gloria
authors.initials: G
authors.lastname: Véliz-Ríos
authors.forename: Regis
authors.initials: R
authors.lastname: Alemán-Zaldívar
authors.forename: M I
authors.initials: MI
authors.lastname: Alonso-Martínez
authors.forename: M
authors.initials: M
authors.lastname: Lago-Baños
authors.forename: N
authors.initials: N
authors.lastname: Puble-Alvarez
authors.forename: A
authors.initials: A
authors.lastname: Delahanty-Fernandez
authors.forename: A I
authors.initials: AI
authors.lastname: Juvier-Madrazo
authors.forename: D
authors.initials: D
authors.lastname: Ortega-León
authors.forename: L
authors.initials: L
authors.lastname: Olivera-Ruano
authors.forename: A
authors.initials: A
authors.lastname: Correa-Fernández
authors.forename: D
authors.initials: D
authors.lastname: Abreu-Reyes
authors.forename: E
authors.initials: E
authors.lastname: Soto-Mestre
authors.forename: M V
authors.initials: MV
authors.lastname: Pérez-Pérez
authors.forename: N
authors.initials: N
authors.lastname: Figueroa-Baile
authors.forename: L Hernandez
authors.initials: LH
authors.lastname: Pérez
authors.forename: A
authors.initials: A
authors.lastname: Rodríguez-Silva
authors.forename: E
authors.initials: E
authors.lastname: Martínez-Díaz
authors.forename: G E
authors.initials: GE
authors.lastname: Guillén-Nieto
authors.forename: Verena L
authors.initials: VL
authors.lastname: Muzio-González
mesh_terms: D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood; D016667:Bacterial Capsules / Q000008:administration & dosage / Q000276:immunology*; D018073:Haemophilus Vaccines / Q000008:administration & dosage / Q000276:immunology*; D019741:Haemophilus influenzae type b / Q000276:immunology; D006510:Hepatitis B Antibodies / Q000097:blood / Q000276:immunology; D017325:Hepatitis B Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology; D006801:Humans; D012449:Safety; D017778:Vaccines, Combined / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D000907:Antibodies, Bacterial; D018073:Haemophilus Vaccines; C044237:Haemophilus influenzae type b polysaccharide vaccine; D006510:Hepatitis B Antibodies; D017325:Hepatitis B Vaccines; D017778:Vaccines, Combined; D014614:Vaccines, Synthetic