Dataset Information

Extrapolating theoretical efficacy of inactivated influenza A/H5N1 virus vaccine from human immunogenicity studies.

ABSTRACT: Influenza A virus subtype H5N1 has been a public health concern for almost 20years due to its potential ability to become transmissible among humans. Phase I and II clinical trials have assessed safety, reactogenicity and immunogenicity of inactivated influenza A/H5N1 virus vaccines. A shortage of vaccine is likely to occur during the first months of a pandemic. Hence, determining whether to give one dose to more people or two doses to fewer people to best protect the population is essential. We use hemagglutination-inhibition antibody titers as an immune correlate for avian influenza vaccines. Using an established relationship to obtain a theoretical vaccine efficacy from immunogenicity data from thirteen arms of six phase I and phase II clinical trials of inactivated influenza A/H5N1 virus vaccines, we assessed: (1) the proportion of theoretical vaccine efficacy achieved after a single dose (defined as primary response level), and (2) whether theoretical efficacy increases after a second dose, with and without adjuvant. Participants receiving vaccine with AS03 adjuvant had higher primary response levels (range: 0.48-0.57) compared to participants receiving vaccine with MF59 adjuvant (range: 0.32-0.47), with no observed trends in primary response levels by antigen dosage. After the first and second doses, vaccine with AS03 at dosage levels 3.75, 7.5 and 15mcg had the highest estimated theoretical vaccine efficacy: Dose (1) 45% (95% CI: 36-57%), 53% (95% CI: 42-63%) and 55% (95% CI: 44-64%), respectively and Dose (2) 93% (95% CI: 89-96%), 97% (95% CI: 95-98%) and 97% (95% CI: 96-100%), respectively. On average, the estimated theoretical vaccine efficacy of lower dose adjuvanted vaccines (AS03 and MF59) was 17% higher than that of higher dose unadjuvanted vaccines, suggesting that including an adjuvant is dose-sparing. These data indicate adjuvanted inactivated influenza A/H5N1 virus vaccine produces high theoretical efficacy after two doses to protect individuals against a potential avian influenza pandemic.

SUBMITTER: Feldstein LR

PROVIDER: S-EPMC5168719 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Extrapolating theoretical efficacy of inactivated influenza A/H5N1 virus vaccine from human immunogenicity studies.

Feldstein Leora R LR Matrajt Laura L Elizabeth Halloran M M Keitel Wendy A WA Longini Ira M IM

Vaccine 20160620 33

Influenza A virus subtype H5N1 has been a public health concern for almost 20years due to its potential ability to become transmissible among humans. Phase I and II clinical trials have assessed safety, reactogenicity and immunogenicity of inactivated influenza A/H5N1 virus vaccines. A shortage of vaccine is likely to occur during the first months of a pandemic. Hence, determining whether to give one dose to more people or two doses to fewer people to best protect the population is essential. We ...[more]

PMID: 27268778

Similar Datasets

Project description:In order to produce a dually effective vaccine against H9 and H5 avian influenza viruses that aligns with the DIVA (differentiating infected from vaccinated animals) strategy, we generated a chimeric H9/H5N2 recombinant vaccine that expressed the whole HA1 region of A/CK/Korea/04163/04 (H9N2) and the HA2 region of recent highly pathogenic avian influenza (HPAI) A/MD/Korea/W452/14 (H5N8) viruses. The chimeric H9/H5N2 virus showed in vitro and in vivo growth properties and virulence that were similar to those of the low-pathogenic avian influenza (LPAI) H9 virus. An inactivated vaccine based on this chimeric virus induced serum neutralizing (SN) antibodies against both H9 and H5 viruses but induced cross-reactive hemagglutination inhibition (HI) antibody only against H9 viruses. Thus, this suggests its compatibility for use in the DIVA strategy against H5 strains. Furthermore, the chimeric H9/H5N2 recombinant vaccine protected immunized chickens against lethal challenge by HPAI H5N8 viruses and significantly attenuated virus shedding after infection by both H9N2 and HPAI H5N8 viruses. In mice, serological analyses confirmed that HA1- and HA2 stalk-specific antibody responses were induced by vaccination and that the DIVA principle could be employed through the use of an HI assay against H5 viruses. Furthermore, each HA1- and HA2 stalk-specific antibody response was sufficient to inhibit viral replication and protect the chimeric virus-immunized mice from lethal challenge with both mouse-adapted H9N2 and wild-type HPAI H5N1 viruses, although differences in vaccine efficacy against a homologous H9 virus (HA1 head domain immune-mediated protection) and a heterosubtypic H5 virus (HA2 stalk domain immune-mediated protection) were observed. Taken together, these results demonstrate that the novel chimeric H9/H5N2 recombinant virus is a low-pathogenic virus, and this chimeric vaccine is suitable for a DIVA vaccine with broad-spectrum neutralizing antibody against H5 avian influenza viruses.IMPORTANCE Current influenza virus killed vaccines predominantly induce antihemagglutinin (anti-HA) antibodies that are commonly strain specific in that the antibodies have potent neutralizing activity against homologous strains but do not cross-react with HAs of other influenza virus subtypes. In contrast, the HA2 stalk domain is relatively well conserved among subtypes, and recently, broadly neutralizing antibodies against this domain have been isolated. Therefore, in light of the need for a vaccine strain that applies the DIVA strategy utilizing an HI assay and induces broad cross-protection against H5N1 and H9N2 viruses, we generated a novel chimeric H9/H5N1 virus that expresses the entire HA1 portion from the H9N2 virus and the HA2 region of the heterosubtypic H5N8 virus. The chimeric H9/H5N2 recombinant vaccine protected immunized hosts against lethal challenge with H9N2 and HPAI H5N1 viruses with significantly attenuated virus shedding in immunized hosts. Therefore, this chimeric vaccine is suitable as a DIVA vaccine against H5 avian influenza viruses.

Dataset Information

Extrapolating theoretical efficacy of inactivated influenza A/H5N1 virus vaccine from human immunogenicity studies.

Publications

Extrapolating theoretical efficacy of inactivated influenza A/H5N1 virus vaccine from human immunogenicity studies.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets