Safety and immunogenicity of influenza A H5 subunit vaccines: effect of vaccine schedule and antigenic variant.

Division of Infectious Diseases and Immunology, Saint Louis University School of Medicine, St. Louis, Missouri 63104, USA.
The Journal of Infectious Diseases (Impact Factor: 5.85). 03/2011; 203(5):666-73. DOI: 10.1093/infdis/jiq093
Source: PubMed

ABSTRACT The current US national stockpile of influenza H5 vaccine was produced using the antigen from the strain A/Vietnam/1203/2004 (a clade 1 H5 virus). Recent H5 disease has been caused by antigenically divergent H5 viruses, including A/Indonesia/05/2005 (a clade 2 H5 virus).
The influence of schedule on the antibody response to 2 doses of H5 vaccines (one a clade 1 hemagglutinin protein [HA] vaccine and one a clade 2 HA vaccine) containing 90 μg of antigen was evaluated in healthy adults 18-49 years of age.
Two doses of vaccine were required to induce antibody titers ≥ 1:10 in most subjects. Accelerated schedules were immunogenic, and antibody developed after vaccinations on days 0 and 7, 0 and 14, and 0 and 28, with the day 0 and 7 schedule inducing lower titers than those induced with the other schedules. With mixed vaccine schedules of clade 1 followed by clade 2 vaccine administration, the first vaccination primed for a heterologous boost. The heterologous response was improved when the second vaccination was given 6 months after the first, compared with the response when the second vaccination was given after an interval of 1 month.
An accelerated vaccine schedule of injections administered at days 0 and 14 was as immunogenic as a vaccine schedule of injections at days 0 and 28, but both schedules were inferior to a vaccine schedule of injections administered at 0 and 6 months for priming for heterologous vaccine boosting. Clinical Trial Registry Number: NCT00703053.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Recent cases of avian influenza H7N9 have caused great concerns that virus may become transmittable between humans. It is imperative to develop an effective vaccine to fight against the pandemic potential of this H7N9 influenza virus to protect human from the disease. This study aims to investigate an optimized formulation for the development of H7N9 vaccines. Various doses of H7N9 inactivated whole or split-virus antigens (0.5, 1.5, or 3 μg based on hemagglutinin content) combined with squalene-based adjuvant (AddaVAX), aluminum hydroxide Al(OH)3 or without adjuvant were evaluated for the efficacy of H7N9 vaccine regiments in mice. With either H7N9 whole or split-virus based vaccines, AddaVAX-adjuvanted formulations were the most immunogenic in eliciting significant humoral immune response against H7N9 virus and exhibited strong cross-reactive response in hemagglutination inhibition (HAI) and viral-neutralization assays against H7N7 virus as well. In contrast, formulations with Al(OH)3 or without adjuvant were less immunogenic and elicited lower titers of HAI and microneutralization assays against both viruses. Dose-sparing experiments suggested that the formulation with as low as 0.004 μg of split or whole virus vaccine antigens together with 50% AddaVAX provided sufficient sero-protective HAI titers and achieved essential virus-neutralizing antibody titers against H7-subtype influenza viruses in mice. Protection experiments demonstrated that the formulation of 0.004 μg to 0.5 μg of split-virion vaccines with AddaVAX conferred full protection against viral challenge up to 100 X LD50 of wild-type H7N9 virus, with 0% survival in placebo group. Taken together, our study demonstrates that squalene-based adjuvant can significantly enhance the protective efficacy of H7N9 virus vaccine and provides a useful strategy to confront the potential pandemic outbreaks of H7N9 virus.
    Vaccine 07/2014; · 3.49 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The best approach to control the spread of influenza virus during a pandemic is vaccination. Yet, an appropriate vaccine is not available early in the pandemic since vaccine production is time consuming. For influenza strains with a high pandemic potential like H5N1, stockpiling of vaccines has been considered but is hampered by rapid antigenic drift of the virus. It has, however, been shown that immunization with a given H5N1 strain can prime the immune system for a later booster with a drifted variant. Here, we investigated whether whole inactivated virus (WIV) vaccine can be processed to tablets suitable for sublingual (s.l.) use and whether s.l. vaccine administration can prime the immune system for a later intramuscular (i.m.) boost with a heterologous vaccine. In vitro results demonstrate that freeze-drying and tableting of WIV did not affect the integrity of the viral proteins or the hemagglutinating properties of the viral particles. Immunization experiments revealed that s.l. priming with WIV (prepared from the H5N1 vaccine strain NIBRG-14) 4 weeks prior to i.m. booster immunization with the same virus strongly enhanced hemagglutination-inhibition (HI) titers against NIBRG-14 and the drifted variant NIBRG-23. Moreover, s.l. (and i.m.) immunization with NIBRG-14 also primed for a subsequent heterologous i.m. booster immunization with NIBRG-23 vaccine. In addition to HI serum antibodies, s.l. priming enhanced lung and nose IgA responses, while i.m. priming enhanced lung IgA but not nose IgA levels. Our results identify s.l. vaccination as a user-friendly method to prime for influenza-specific immune responses toward homologous and drifted variants.
    The AAPS Journal 01/2014; · 3.91 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A variety of platforms are being explored for the development of vaccines for pandemic influenza. Observations that traditional inactivated subvirion vaccines and live-attenuated vaccines against H5 and some H7 influenza viruses were poorly immunogenic spurred efforts to evaluate new approaches, including whole virus vaccines, higher doses of antigen, addition of adjuvants and combinations of different vaccine modalities in heterologous prime-boost regimens to potentiate immune responses. Results from clinical trials of prime-boost regimens have been very promising. Further studies are needed to determine optimal combinations of platforms, intervals between doses of vaccines and the logistics of deployment in pre-pandemic and early pandemic settings.
    Expert Review of Vaccines 05/2014; · 4.22 Impact Factor

Full-text (2 Sources)

Available from
May 27, 2014

Similar Publications