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A phase I evaluation of inactivated influenza A/H5N1 vaccine administered by the intradermal or the intramuscular route.

ABSTRACT: In a phase I clinical trial, one hundred healthy young adults were randomized to receive two doses 28 days apart of an inactivated, subvirion vaccine containing 15 or 45microg of influenza A/H5N1 hemagglutinin (HA) by the intramuscular (IM) route, or 3 or 9microg of H5 HA by the intradermal(ID) route. Seventy-seven subjects received a third dose. All regimens were safe and well tolerated. Antibody responses after two or three doses were low (

SUBMITTER: Patel SM

PROVIDER: S-EPMC2913582 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature

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A phase I evaluation of inactivated influenza A/H5N1 vaccine administered by the intradermal or the intramuscular route.

Patel Shital M SM Atmar Robert L RL El Sahly Hana M HM Cate Thomas R TR Keitel Wendy A WA

Vaccine 20091118 17

In a phase I clinical trial, one hundred healthy young adults were randomized to receive two doses 28 days apart of an inactivated, subvirion vaccine containing 15 or 45microg of influenza A/H5N1 hemagglutinin (HA) by the intramuscular (IM) route, or 3 or 9microg of H5 HA by the intradermal(ID) route. Seventy-seven subjects received a third dose. All regimens were safe and well tolerated. Antibody responses after two or three doses were low (<or=20% or <or=38%, respectively) and similar in group ...[more]

PMID: 19931380

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Project description:During the past decade, a number of H5 subtype influenza vaccines have been developed and tested in clinical trials, but most of them induced poor serum antibody responses prompting the evaluation of novel vaccination approaches. One of the most promising ones is a "prime-boost" strategy, which could result in the induction of prompt and robust immune responses to a booster influenza vaccine following priming with homologous or heterologous vaccine strains. In our study we evaluated immunogenicity of an adjuvanted A(H5N1) inactivated influenza vaccine (IIV) in healthy adult subjects who received A(H5N2) live attenuated influenza vaccine (LAIV) 1.5 years earlier and compared this with a group of naïve subjects. We found that priming with A(H5N2) LAIV induced a long-lasting B-cell immunological memory against influenza A(H5N1) virus, which was brought on by more prompt and vigorous antibody production to a single dose of A(H5N1) IIV in the primed group, compared to the naïve controls. Thus, by day 28 after the first booster dose, the hemagglutination inhibition and neutralizing (MN) antibody titer rises were 17.2 and 30.8 in the primed group, compared to 2.3 and 8.0 in the control group, respectively. The majority (79%) of the primed individuals achieved seroprotective MN antibody titers at 7 days after the first dose of the IIV. All LAIV-primed volunteers had MN titers ? 1:40 by Day 28 after one dose of IIV, whereas only 58% subjects from the naïve control group developed similar immune responses at this time point. The second A(H5N1) IIV dose did not increase the immune response in the LAIV-primed group, whereas 2 doses of IIV were required for naïve volunteers to develop significant immune responses. These findings were of special significance since Russian-based LAIV technology has been licensed to WHO, through whom the vaccine has been provided to vaccine manufacturers in India, China and Thailand - countries particularly vulnerable to a pandemic influenza. The results of our study will be useful to inform the development of vaccination strategies in these countries in the event of a pandemic.

Project description: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.

Dataset Information

A phase I evaluation of inactivated influenza A/H5N1 vaccine administered by the intradermal or the intramuscular route.

Publications

A phase I evaluation of inactivated influenza A/H5N1 vaccine administered by the intradermal or the intramuscular route.

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