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      Broad Clade 2 Cross-Reactive Immunity Induced by an Adjuvanted Clade 1 rH5N1 Pandemic Influenza Vaccine

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          Abstract

          Background

          The availability of H5N1 vaccines that can elicit a broad cross-protective immunity against different currently circulating clade 2 H5N1 viruses is a pre-requisite for the development of a successful pre-pandemic vaccination strategy. In this regard, it has recently been shown that adjuvantation of a recombinant clade 1 H5N1 inactivated split-virion vaccine with an oil-in-water emulsion-based adjuvant system also promoted cross-immunity against a recent clade 2 H5N1 isolate (A/Indonesia/5/2005, subclade 2.1). Here we further analyse the cross-protective potential of the vaccine against two other recent clade 2 isolates (A/turkey/Turkey/1/2005 and A/Anhui/1/2005 which are, as defined by WHO, representatives of subclades 2.2 and 2.3 respectively).

          Methods and Findings

          Two doses of the recombinant A/Vietnam/1194/2004 (H5N1, clade 1) vaccine were administered 21 days apart to volunteers aged 18–60 years. We studied the cross-clade immunogenicity of the lowest antigen dose (3.8 µg haemagglutinin) given with (N = 20) or without adjuvant (N = 20). Immune responses were assessed at 21 days following the first and second vaccine doses and at 6 months following first vaccination. Vaccination with two doses of 3.8 µg of the adjuvanted vaccine induced four-fold neutralising seroconversion rates in 85% of subjects against A/turkey/Turkey/1/2005 (subclade 2.2) and 75% of subjects against A/Anhui/1/2005 (subclade 2.3) recombinant strains. There was no response induced against these strains in the non-adjuvanted group. At 6 months following vaccination, 70% and 60% of subjects retained neutralising antibodies against the recombinant subclade 2.2 and 2.3 strains, respectively and 40% of subjects retained antibodies against the recombinant subclade 2.1 A/Indonesia/5/2005 strain.

          Conclusions

          In addition to antigen dose-sparing, adjuvantation of inactivated split H5N1 vaccine promotes broad and persistent cross-clade immunity which is a pre-requisite for a pre-pandemic vaccine.

          Trial Registration

          ClinicalTrials.gov NCT00309634

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          Mitigation strategies for pandemic influenza in the United States.

          Timothy Germann, Kai Kadau, Ira Longini … (2006)
          Recent human deaths due to infection by highly pathogenic (H5N1) avian influenza A virus have raised the specter of a devastating pandemic like that of 1917-1918, should this avian virus evolve to become readily transmissible among humans. We introduce and use a large-scale stochastic simulation model to investigate the spread of a pandemic strain of influenza virus through the U.S. population of 281 million individuals for R(0) (the basic reproductive number) from 1.6 to 2.4. We model the impact that a variety of levels and combinations of influenza antiviral agents, vaccines, and modified social mobility (including school closure and travel restrictions) have on the timing and magnitude of this spread. Our simulations demonstrate that, in a highly mobile population, restricting travel after an outbreak is detected is likely to delay slightly the time course of the outbreak without impacting the eventual number ill. For R(0) < 1.9, our model suggests that the rapid production and distribution of vaccines, even if poorly matched to circulating strains, could significantly slow disease spread and limit the number ill to <10% of the population, particularly if children are preferentially vaccinated. Alternatively, the aggressive deployment of several million courses of influenza antiviral agents in a targeted prophylaxis strategy may contain a nascent outbreak with low R(0), provided adequate contact tracing and distribution capacities exist. For higher R(0), we predict that multiple strategies in combination (involving both social and medical interventions) will be required to achieve similar limits on illness rates.
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            Characterization of an avian influenza A (H5N1) virus isolated from a child with a fatal respiratory illness.

            K. Subbarao, A. Klimov, J. Katz … (1998)
            An avian H5N1 influenza A virus (A/Hong Kong/156/97) was isolated from a tracheal aspirate obtained from a 3-year-old child in Hong Kong with a fatal illness consistent with influenza. Serologic analysis indicated the presence of an H5 hemagglutinin. All eight RNA segments were derived from an avian influenza A virus. The hemagglutinin contained multiple basic amino acids adjacent to the cleavage site, a feature characteristic of highly pathogenic avian influenza A viruses. The virus caused 87.5 to 100 percent mortality in experimentally inoculated White Plymouth Rock and White Leghorn chickens. These results may have implications for global influenza surveillance and planning for pandemic influenza.
            Article 0 comments Cited 315 times – based on 0 reviews     Review now
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              Probable person-to-person transmission of avian influenza A (H5N1).

              Kumnuan Ungchusak, Prasert Auewarakul, Scott Dowell … (2005)
              During 2004, a highly pathogenic avian influenza A (H5N1) virus caused poultry disease in eight Asian countries and infected at least 44 persons, killing 32; most of these persons had had close contact with poultry. No evidence of efficient person-to-person transmission has yet been reported. We investigated possible person-to-person transmission in a family cluster of the disease in Thailand. For each of the three involved patients, we reviewed the circumstances and timing of exposures to poultry and to other ill persons. Field teams isolated and treated the surviving patient, instituted active surveillance for disease and prophylaxis among exposed contacts, and culled the remaining poultry surrounding the affected village. Specimens from family members were tested by viral culture, microneutralization serologic analysis, immunohistochemical assay, reverse-transcriptase-polymerase-chain-reaction (RT-PCR) analysis, and genetic sequencing. The index patient became ill three to four days after her last exposure to dying household chickens. Her mother came from a distant city to care for her in the hospital, had no recognized exposure to poultry, and died from pneumonia after providing 16 to 18 hours of unprotected nursing care. The aunt also provided unprotected nursing care; she had fever five days after the mother first had fever, followed by pneumonia seven days later. Autopsy tissue from the mother and nasopharyngeal and throat swabs from the aunt were positive for influenza A (H5N1) by RT-PCR. No additional chains of transmission were identified, and sequencing of the viral genes identified no change in the receptor-binding site of hemagglutinin or other key features of the virus. The sequences of all eight viral gene segments clustered closely with other H5N1 sequences from recent avian isolates in Thailand. Disease in the mother and aunt probably resulted from person-to-person transmission of this lethal avian influenzavirus during unprotected exposure to the critically ill index patient. Copyright 2005 Massachusetts Medical Society.
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                Author and article information

                Contributors
                : Role: Academic Editor
                Journal
                Journal ID (nlm-ta): PLoS ONE
                Journal ID (publisher-id): plos
                Journal ID (pmc): plosone
                Title: PLoS ONE
                Publisher: Public Library of Science (San Francisco, USA )
                ISSN (Electronic): 1932-6203
                Publication date Collection: 2008
                Publication date (Electronic): 27 February 2008
                Volume: 3
                Issue: 2
                Electronic Location Identifier: e1665
                Affiliations
                [1 ]Centre for Vaccinology, Ghent University and Hospital, Ghent, Belgium
                [2 ]GlaxoSmithKline Biologicals, Dresden, Germany
                [3 ]GlaxoSmithKline Biologicals, Rixensart, Belgium
                Federal University of Sao Paulo, Brazil
                Author notes

                Conceived and designed the experiments: EH GL IL RB PG MD. Performed the experiments: RB PG. Analyzed the data: EH GL IL RB PG MD. Contributed reagents/materials/analysis tools: EH GL IL RB PG. Wrote the paper: EH GL IL RB PG MD.

                Article
                Publisher ID: 07-PONE-CT-02540R1
                DOI: 10.1371/journal.pone.0001665
                PMC ID: 2253495
                PubMed ID: 18301743
                SO-VID: 90c55d2e-147a-477e-83ae-8345e7afbe46
                Copyright © Leroux-Roels et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                Date received : 21 October 2007
                Date accepted : 9 January 2008
                Page count
                Pages: 5
                Categories
                Subject: Research Article
                Subject: Immunology/Immune Response
                Subject: Immunology/Immunity to Infections
                Subject: Infectious Diseases/Epidemiology and Control of Infectious Diseases
                Subject: Infectious Diseases/Viral Infections

                ScienceOpen disciplines: Uncategorized
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                ScienceOpen disciplines: Uncategorized

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