Assessment of squalene adjuvanted and non-adjuvanted vaccines against pandemic H1N1 influenza in children 6 months to 17 years of age.

Vaccines were urgently needed in 2009 against A/H1N1 pandemic influenza. Based on the H5N1 experience, it was originally thought that 2 doses of an adjuvanted vaccine were needed for adequate immunogenicity. We tested H1N1 vaccines with or without AF03, a squalene-based adjuvant, in children.

Safety and immunogenicity of three different formulations of a liquid hexavalent diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae b conjugate-hepatitis B vaccine at 2, 4, 6 and 12-14 months of age.

The current recommended infant vaccination schedules require many injections at multiple sites, which increase stress for infants and parents and may create challenges to vaccination compliance. Therefore, combination vaccines, which reduce the number of injections at each medical visit, can be an essential method to improve compliance. The objective of this study was to assess the safety and immunogenicity of an investigational, liquid, hexavalent, pediatric vaccine at 2, 4, 6, and 12-14 months of age.

AF03-adjuvanted and non-adjuvanted pandemic influenza A (H1N1) 2009 vaccines induce strong antibody responses in seasonal influenza vaccine-primed and unprimed mice.

Pandemic influenza vaccines have been manufactured using the A/California/07/2009 (H1N1) strain as recommended by the World Health Organization. We evaluated in mice the immunogenicity of pandemic (H1N1) 2009 vaccine and the impact of prior vaccination against seasonal trivalent influenza vaccines (TIV) on antibody responses against pandemic (H1N1) 2009. In naïve mice, a single dose of unadjuvanted H1N1 vaccine (3 microg of HA) was shown to elicit hemagglutination inhibition (HI) antibody titers >40, a titer associated with protection in humans against seasonal influenza.

Improving seasonal and pandemic influenza vaccines.

Challenges facing seasonal and pandemic influenza vaccination include: increasing the immunogenicity of seasonal vaccines for the most vulnerable, increasing vaccination coverage against seasonal influenza, and developing vaccines against pandemic strains that are immunogenic with very low quantities of antigen to maximize the number of people who can be vaccinated with a finite production capacity. We review Sanofi Pasteur's epidemic and pandemic influenza research and development programmes with emphasis on two key projects: intradermal influenza vaccine for seasonal vaccination of both elderly and younger adults, and pandemic influenza vaccine.

Safety and immunogenicity of a hexavalent diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae b conjugate-hepatitis B vaccine at 2, 3, 4, and 12-14 months of age.

Combination vaccines improve parental and provider satisfaction and schedule compliance by decreasing the number of injections. In a Phase 2, randomized, double-blind, multicenter study, we compared four formulations of a liquid, hexavalent diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae b conjugate-hepatitis B virus (DTaP-IPV-Hib-HBV) vaccine in 708 infants immunized at 2, 3, 4, and 12-14 months of age. The formulations contained identical DTaP and IPV components, differing in the contents of Hib polyribosylribitol phosphate (PRP) conjugate component (tetanus-toxoid [PRP-T, 12microg] or Neisseria meningitidis outer-membrane-protein-complex [PRP-OMPC, 3microg or 6microg]), and in hepatitis B surface antigen (HBsAg, 10microg or 15microg).

Safety and immunogenicity of two formulations of a hexavalent diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae conjugate-hepatitis B vaccine in 15 to 18-month-old children.

Combination vaccines decrease the number of injections and improve parental satisfaction and vaccination schedule compliance. In a phase 1, randomized, partially-blinded, single-dose booster study, we evaluated two formulations of an investigational liquid hexavalent vaccine containing diphtheria, tetanus, acellular pertussis (5-component), inactivated poliovirus, Haemophilus influenzae b conjugate and hepatitis B surface antigen (DTaP-IPV-Hib-HBV) in 60 healthy toddlers, 15 to 18 months of age, who had been primed with three doses of a licensed pentavalent diphtheria, tetanus, acellular pertussis (5-component), inactivated poliovirus, Haemophilus influenzae b conjugate (DTaP-IPV//PRP-T) vaccine. The DTaP-IPV//PRP-T vaccine was used as a control in 30 subjects.

Lot-to-lot consistency of a combined hexavalent diptheria-tetanus-acellular-pertussis, hepatitis B, Inactivated polio and haemophilus B conjugate vaccine, administered to healthy chilean infants at two, four and six months of age.

Objectives: To assess the safety, immunogenicity and lot consistency of a liquid hexavalent combined vaccine (DTaP-IPV-PRP approximately T-HBs, HEXAVAC) (Sanofi-Pasteur MSD, France) administered to infants at two, four and six months of age.

Methods: A total of 1028 infants were vaccinated with one of three vaccine lots, in a randomized, double-blind fashion. Equivalence testing was used to compare post-vaccination seroprotection/seroconversion rates and geometric mean titers (GMTs) for each antigen between the three lots.

A liquid hexavalent combined vaccine against diphtheria, tetanus, pertussis, poliomyelitis, Haemophilus influenzae type B and hepatitis B: review of immunogenicity and safety.

To reduce the number of injections needed to comply with paediatric vaccination requirements, a liquid, hexavalent vaccine (DTaP-IPV-PRP-T-HBs; Hexavac; Aventis Pasteur MSD) has been developed for primary and booster vaccination of infants and toddlers. In extensive clinical studies, Hexavac has been shown to be highly immunogenic. Seroconversion or seroprotective titres of antibodies against all antigens were achieved in the majority of infants following a primary series of three doses administered at 1-2-month intervals from 2 months of age.

Haemophilus influenzae type b vaccine: reconstitution of lyophilised PRP-T vaccine with a pertussis-containing paediatric combination vaccine, or a change in the primary series immunisation schedule, may modify the serum anti-PRP antibody responses.

Immunogenicity data obtained after primary series immunisations against Haemophilus influenzae type b (Hib), using a vaccine prepared by conjugating the capsular polysaccharide of Hib to tetanus toxoid (ActHIB), were compiled from 146 study groups comprising 85 clinical trials or vaccination programs conducted between 1987 and 1999. ActHIB was administered as a monovalent lyophilised vaccine, injected either in association with another paediatric vaccine (at separate administration sites) or in combination (where the different vaccines are mixed together in the same syringe before injection). Review of these data reveals two trends.

Large scale safety study of a liquid hexavalent vaccine (D-T-acP-IPV-PRP--T-HBs) administered at 2, 4, 6 and 12-14 months of age.

A study was conducted to assess the safety of a new, liquid hexavalent vaccine (Hexavac, Aventis Pasteur MSD, Lyon, France) in a large population of 1783 children in Germany vaccinated at 2, 4, 6 and 12-14 months of age. Immediate reactions, local and systemic reactions, and serious adverse events (SAEs) were monitored. The frequencies of redness > or = 2 cm and swelling > or = 2 cm were 6.

Immunogenicity and safety of a new liquid hexavalent combined vaccine compared with separate administration of reference licensed vaccines in infants.

Objective: The immunogenicity and safety of a new liquid hexavalent vaccine (diphtheria-tetanus-acellular pertussis-inactivated polio vaccine-hepatitis B-polyribosyl ribitol phosphate conjugated to tetanus protein; Hexavac; Aventis Pasteur MSD, Lyon, France) are compared with those of reference vaccines [diphtheria-tetanus-acellular pertussis-inactivated polio vaccine reconstituting lyophilized purified Haemophilus influenzae polysaccharide conjugated to tetanus protein vaccine (Pentavac; Aventis Pasteur MSD) and hepatitis B vaccine (H-B-Vax II; Aventis Pasteur MSD)] injected separately at the same visit in a prospective multicenter, comparative, open label trial.

Methods: Infants were randomized to receive Hexavac (n = 423) or Pentavac and H-B-Vax II (n = 425) as a primary immunization series at 2, 4 and 6 months of age. Seroprotection and seroconversion rates against all antigens at 1 month after the primary series were compared between the two vaccine groups with 95% confidence intervals (CI0.

New acellular pertussis-containing paediatric combined vaccines.

Combined pediatric vaccines have the advantages of conferring protection against multiple common infectious diseases with a reduced number of injections. Their use should lead to better compliance to recommended vaccination schedules. Diphtheria (D), tetanus (T) and whole-cell pertussis vaccine (P) have been successfully combined, with or without inactivated poliovirus vaccine (IPV) in the same syringe for many years.

Randomised study of the possible adjuvant effect of BCG vaccine on the immunogenicity of diphtheria-tetanus-acellular pertussis vaccine in Senegalese infants.

Following a study in Senegal (1990-1995) in which the relative efficacy of a diphtheria-tetanus-acellular pertussis vaccine (DTaP) was compared with that of a diphtheria-tetanus-whole-cell pertussis vaccine in children given a simultaneous injection of Bacille Calmette-Guérin (BCG) vaccine, this subsequent study was conducted to evaluate the possible adjuvant effect of the BCG vaccine on acellular pertussis vaccine components. A second objective was to compare the immunogenicity of these components when administered in accordance with a 2-4-6-month (spaced) schedule or an accelerated 2-3-4-month schedule. In all, 390 healthy Senegalese infants were randomly divided into three groups of 130 infants.

Safety and immunogenicity of a combined diphtheria-tetanus-acellular pertussis-inactivated polio vaccine-Haemophilus influenzae type b vaccine administered at 2-4-6-13 or 3-5-12 months of age.

Methods: In an open randomized study we compared the safety and immunogenicity of two schedules for priming and booster vaccinations of infants. A pentavalent combination vaccine, including a lyophilized Haemophilus influenzae type b-tetanus toxoid conjugate vaccine reconstituted with a liquid diphtheria, tetanus, acellular pertussis (pertussis toxoid and filamentous hemagglutinin) and inactivated polio vaccine (DTaP-IPV/Act-HIB; Pasteur Mérieux Connaught, Lyon, France) was administered to 236 Swedish infants either at 2, 4 and 6 months or at 3 and 5 months, and a booster dose was administered 7 months after the last primary dose. Adverse events were monitored by diaries for 3 days after each vaccination and by questions at the ensuing visits.

Clinical acceptability and immunogenicity of a pentavalent parenteral combination vaccine containing diphtheria, tetanus, acellular pertussis, inactivated poliomyelitis and Haemophilus influenzae type b conjugate antigens in two-, four- and six-month-old Chilean infants.

Background: In recent years additional parenteral vaccines have been recommended for routine immunization of infants in the US and elsewhere. The ability to administer multiple vaccines as a single injection without unacceptably increasing reactogenicity or decreasing immunogenicity of any component would offer many practical advantages.

Methods: A randomized, open, controlled trial was conducted to assess the tolerance profile and immunogenicity, as well as to identify potential antigenic interferences, resulting from administration of a parenteral combination vaccine for infants.

A randomized double-blind trial comparing a two-component acellular to a whole-cell pertussis vaccine in Senegal.

A randomized, double-blind trial comparing a diphtheria-tetanus-acellular pertussis vaccine (DTaP) (pertussis toxoid and filamentous hemagglutinin) with a whole-cell vaccine (DTwP) was conducted. A case-contact study was nested in the trial to estimate absolute efficacy. From 1990 through 1994, 4181 children were randomized to receive one of the vaccines at 2, 4, and 6 months.

Characterization of minor and major antigenic regions within the hepatitis B virus nucleocapsid.

Hepatitis B core antibodies (anti-HBc) appear very early during the course of the hepatitis B virus infection and often persist years after viral clearance. In order to characterize the immunodominant domain of the HBcAg, the human immune response against the HBV nucleocapsid (HBcAg) was analyzed by using 14 synthetic peptides. Anti-HBc antibodies were detected by an indirect enzyme-linked immunosorbent assay (ELISA) with HBc peptides.

Specific detection of anti-HBc antibodies with an enzyme immunoassay using recombinant HBcAg and monoclonal antibodies.

An enzyme immunoassay for the detection of total anti-HBc antibodies in undiluted serum samples was developed. This assay utilizes an anti-HBc monoclonal antibody and a recombinant HBc antigen. The results of the clinical validation are now reported.

HIV-1 env, nef, and gag-specific T-cell immunity in mice: conserved epitopes in nef p27 and gag p25 proteins.

Cellular immunogenicity of env gp160, nef p27, and gag p55 proteins of human immunodeficiency virus type 1 (HIV-1) was studied in mice immunized with vaccinia virus recombinants. Proliferative responses of spleen cells were comparable against env gp160, nef p27, and gag p25 recombinant proteins. No specific activity was observed against gag p18 protein.

Enhancement of HIV-specific cytotoxic T lymphocyte responses by zidovudine (AZT) treatment.

Zidovudine or 3'-azido-2'-3'-dideoxy-thymidine (AZT) is an antiviral drug widely used to treat HIV-infected patients. Because cytotoxic T lymphocytes (CTL) are thought to contribute actively to resistance against HIV-induced disease, we studied sequentially 10 HIV-infected individuals under zidovudine treatment for a period of 6-12 months. For a given patient all lymphocyte suspensions corresponding to the complete zidovudine therapy period were tested on the same day and on the same target cells.

Multiple subsets of HIV-specific cytotoxic T lymphocytes in humans and in mice.

The human immunodeficiency virus type 1 (HIV-1) induces a strong cytotoxic T lymphocyte (CTL) response in humans following infection. HIV-specific CTL can be detected directly in the blood and lungs of infected patients, and can be expanded in vitro by stimulation with autologous HIV-infected lymphoblasts. Furthermore, CTL specific for HIV envelope glycoprotein gp160 have been obtained in mice by immunization with recombinant vaccinia virus (VV) that carry the HIV env gene.

Unusually high frequencies of HIV-specific cytotoxic T lymphocytes in humans.

CTL specific for the HIV belong to the CD8 subset of T lymphocytes, and their activity is restricted by class I HLA transplantation Ag. In this report, HIV-specific CTL and their precursor cells were quantified by limiting dilution analysis. CTL were recovered from the lungs, lymph nodes, and blood of asymptomatic seropositive carriers and of patients with AIDS.

Cytotoxic T lymphocytes in HIV-induced disease: implications for therapy and vaccination.

The immune response to HIV in infected humans leads to the production of HIV-specific cytotoxic T lymphocytes (CTL) which circulate in high frequencies. The presence of these CTL and their eventual protective activities have been studied by various laboratories, and correlations have been made with certain immunopathological manifestations of HIV infections. It seems probable that HIV-immune CTL participate in the induction of certain disorders by initiating inflammatory reactions in the lungs, central nervous system and lymph nodes.