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Assessment of the efficacy of commercially available and candidate vaccines against a pandemic H1N1 2009 virus.

ABSTRACT: BACKGROUND:The emergence and global spread of the pandemic H1N1 2009 influenza virus have raised questions regarding the protective effect of available seasonal vaccines and the efficacy of a newly produced matched vaccine. METHODS:Ferrets were immunized with the 2008-2009 formulations of commercially available live attenuated (FluMist; MedImmune) or split-inactivated (Fluviral; GlaxoSmithKline) vaccines, a commercial swine vaccine (FluSure; Pfizer), or a laboratory-produced matched inactivated whole-virus vaccine (A/Mexico/InDRE4487/2009). Adaptive immune responses were monitored, and the animals were challenged with A/Mexico/InDRE4487/2009 after 5 weeks. RESULTS:Only animals that received the swine or matched vaccines developed detectable hemagglutination-inhibiting antibodies against the challenge virus, whereas a T cell response was exclusively detected in animals vaccinated with FluMist. After challenge, all animals had high levels of virus replication in the upper respiratory tract. However, preexisting anti-pandemic H1N1 2009 antibodies resulted in reduced clinical signs and improved survival. Surprisingly, FluMist was associated with a slight increase in mortality and greater lung damage, which correlated with early up-regulation of interleukin-10. CONCLUSIONS:The present study demonstrates that a single dose of matched inactivated vaccine confers partial protection against a pandemic H1N1 2009 virus, and it suggests that a higher dose or prime-boost regimen may be required. The consequences of mismatched immunity to influenza merit further investigation.

SUBMITTER: Kobinger GP

PROVIDER: S-EPMC7109664 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature

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Assessment of the efficacy of commercially available and candidate vaccines against a pandemic H1N1 2009 virus.

Kobinger Gary P GP Meunier Isabelle I Patel Ami A Pillet Stéphane S Gren Jason J Stebner Shane S Leung Anders A Neufeld James L JL Kobasa Darwyn D von Messling Veronika V

The Journal of infectious diseases 20100401 7

<h4>Background</h4>The emergence and global spread of the pandemic H1N1 2009 influenza virus have raised questions regarding the protective effect of available seasonal vaccines and the efficacy of a newly produced matched vaccine.<h4>Methods</h4>Ferrets were immunized with the 2008-2009 formulations of commercially available live attenuated (FluMist; MedImmune) or split-inactivated (Fluviral; GlaxoSmithKline) vaccines, a commercial swine vaccine (FluSure; Pfizer), or a laboratory-produced match ...[more]

PMID: 20170374

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Project description:In June 2009, the World Health Organization declared the first influenza pandemic of the 21st century, due to the emergence and rapid spread of new swine origin H1N1 influenza A virus. In contrast to seasonal influenza infections, which typically cause morbidity and mortality in the elderly, this virus caused severe infection in young adults and not the elderly. This phenomenon was attributed to the presence of cross-neutralizing antibodies acquired by older individuals from previous exposure to swine origin influenza. However, this hypothesis could not be empirically tested using clinical data. To address this question, we investigated viral replication and the development of the immune response in naï12 years old) and aged (20 to 24 years old) female rhesus macaques infected with A/California/04/2009 (H1N1), one of the circulating pandemic strains in 2009. We compared viral loads as well as the kinetics and magnitude of the adaptive immune response in peripheral blood and bronchoalveolar lavage samples (BAL) collected longitudinally for 99 days post-infection. Although, adult animals exhibited earlier T cell responses in peripheral blood, aged animals generated a robust T cell response with comparable kinetics and magnitude as those observed in young animals in BAL. Moreover, aged animals generated a higher hemagglutination inhibition titer compared to young animals. We also measured the concentration of several cytokines in BAL supernatant. With the exception of IL-8, which was higher in aged animals, we found no differences in IFNa, IFNb, TNFa, IL-1r, IL-6, IL-15, IL-17, or MCP1 levels. Finally, we compared gene expression infection using microarray analysis of BAL samples taken on days 0, 4, 7, 10, and 14 pi. Our analyses revealed that the largest difference in host response between aged and young animals was detected day 4 post-infection, with significant enrichment for genes associated with inflammation, the innate immune response, and T cell activation in aged animals. The ability of aged animals to generate a robust immune response, especially antibody response, following infection with 2009 H1N1 virus could explain the lack of morbidity normally observed with seasonal influenza viruses in this vulnerable population.

Project description:BACKGROUND:Although the 2009 (H1N1) influenza pandemic officially ended in August 2010, the virus will probably circulate in future years. Several types of H1N1 vaccines have been tested including various dosages and adjuvants, and meta-analysis is needed to identify the best formulation. METHODS:We searched MEDLINE, EMBASE, and nine clinical trial registries to April 2011, in any language for randomized clinical trials (RCTs) on healthy children, adolescents, adults and the elderly. Primary outcome was the seroconversion rate according to hemagglutinination-inhibition (HI); secondary outcomes were adverse events. For the primary outcome, we used head-to-head meta-analysis and multiple-treatments meta-analysis. RESULTS:Eighteen RCTs could be included in all primary analyses, for a total of 76 arms (16,725 subjects). After 2 doses, all 2009 H1N1 split/subunit inactivated vaccines were highly immunogenic and overcome CPMP seroconversion criteria. After 1 dose only, all split/subunit vaccines induced a satisfactory immunogenicity (>?=?70%) in adults and adolescents, while only some formulations showed acceptable results for children and elderly (non-adjuvanted at high-doses and oil-in-water adjuvanted vaccines). Vaccines with oil-in-water adjuvants were more immunogenic than both nonadjuvanted and aluminum-adjuvanted vaccines at equal doses and their immunogenicity at doses <?=?6 µg (even with as little as 1.875 µg of hemagglutinin antigen) was not significantly lower than that achieved after higher doses. Finally, the rate of serious vaccine-related adverse events was low for all 2009 H1N1 vaccines (3 cases, resolved in 10 days, out of 22826 vaccinated subjects). However, mild to moderate adverse reactions were more (and very) frequent for oil-in-water adjuvanted vaccines. CONCLUSIONS:Several one-dose formulations might be valid for future vaccines, but 2 doses may be needed for children, especially if a low-dose non-adjuvanted vaccine is used. Given that 15 RCTs were sponsored by vaccine manufacturers, future trials sponsored by non-industry agencies and comparing vaccines using different types of adjuvants are needed.

Dataset Information

Assessment of the efficacy of commercially available and candidate vaccines against a pandemic H1N1 2009 virus.

Publications

Assessment of the efficacy of commercially available and candidate vaccines against a pandemic H1N1 2009 virus.

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