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PLoS ONE. Assessment of Human Immune Responses to H7 Avian Influenza Virus of Pandemic Potential: Results from a Placebo?Controlled, Randomized Double?Blind Phase
[Source: PLoS ONE, full page: (LINK). Abstract, edited.]
Open Access / Peer-Reviewed / Research Article
Assessment of Human Immune Responses to H7 Avian Influenza Virus of Pandemic Potential: Results from a Placebo?Controlled, Randomized Double?Blind Phase
Larisa Rudenko, Irina Kiseleva, Anatoly N. Naykhin, Marianna Erofeeva, Marina Stukova, Svetlana Donina, Galina Petukhova, Maria Pisareva, Vera Krivitskaya, Michael Grudinin, Zhanna Buzitskaya, Irina Isakova?Sivak, Svetlana Kuznetsova, [ ... ], Natalie Larionova, Julia Desheva, Irina Dubrovina, Alexandra Nikiforova, John C. Victor, Kathy Neuzil, Jorge Flores, Vadim Tsvetnitsky, Oleg Kiselev
Published: February 12, 2014 / DOI: 10.1371/journal.pone.0087962
Abstract
Introduction
Live attenuated influenza vaccines (LAIVs) are being developed to protect humans against future epidemics and pandemics. This study describes the results of a double?blinded randomized placebo?controlled phase I clinical trial of cold?adapted and temperature sensitive H7N3 live attenuated influenza vaccine candidate in healthy seronegative adults.
Objective
The goal of the study was to evaluate the safety, tolerability, immunogenicity and potential shedding and transmission of H7N3 LAIV against H7 avian influenza virus of pandemic potential.
Methods and Findings
Two doses of H7N3 LAIV or placebo were administered to 40 randomly divided subjects (30 received vaccine and 10 placebo). The presence of influenza A virus RNA in nasal swabs was detected in 60.0% and 51.7% of subjects after the first and second vaccination, respectively. In addition, vaccine virus was not detected among placebo recipients demonstrating the absence of person?to?person transmission. The H7N3 live attenuated influenza vaccine demonstrated a good safety profile and was well tolerated. The two?dose immunization resulted in measurable serum and local antibody production and in generation of antigen?specific CD4<SUP>+</SUP> and CD8<SUP>+</SUP> memory T cells. Composite analysis of the immune response which included hemagglutinin inhibition assay, microneutralization tests, and measures of IgG and IgA and virus?specific T cells showed that the majority (86.2%) of vaccine recipients developed serum and/or local antibodies responses and generated CD4<SUP>+</SUP> and CD8<SUP>+</SUP> memory T cells.
Conclusions
The H7N3 LAIV was safe and well tolerated, immunogenic in healthy seronegative adults and elicited production of antibodies broadly reactive against the newly emerged H7N9 avian influenza virus.
Trial registration
ClinicalTrials.gov NCT01511419
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Citation: Rudenko L, Kiseleva I, Naykhin AN, Erofeeva M, Stukova M, et al. (2014) Assessment of Human Immune Responses to H7 Avian Influenza Virus of Pandemic Potential: Results from a Placebo?Controlled, Randomized Double?Blind Phase I Study of Live Attenuated H7N3 Influenza Vaccine. PLoS ONE 9(2): e87962. doi:10.1371/journal.pone.0087962
Editor: Ernesto T. A. Marques, University of Pittsburgh, United States of America
Received: October 5, 2013; Accepted: December 24, 2013; Published: February 12, 2014
Copyright: ? 2014 Rudenko 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.
Funding: The study was supported by Program for Appropriate Technologies in Health (PATH) (http://sites.path.org/vaccinedevelopment/influenza/). Some funders (VT, JCV, KN, JF) participated in designing the experiments and critically reviewed the manuscript.
Competing interests: The authors have declared that no competing interests exist.
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Open Access / Peer-Reviewed / Research Article
Assessment of Human Immune Responses to H7 Avian Influenza Virus of Pandemic Potential: Results from a Placebo?Controlled, Randomized Double?Blind Phase
Larisa Rudenko, Irina Kiseleva, Anatoly N. Naykhin, Marianna Erofeeva, Marina Stukova, Svetlana Donina, Galina Petukhova, Maria Pisareva, Vera Krivitskaya, Michael Grudinin, Zhanna Buzitskaya, Irina Isakova?Sivak, Svetlana Kuznetsova, [ ... ], Natalie Larionova, Julia Desheva, Irina Dubrovina, Alexandra Nikiforova, John C. Victor, Kathy Neuzil, Jorge Flores, Vadim Tsvetnitsky, Oleg Kiselev
Published: February 12, 2014 / DOI: 10.1371/journal.pone.0087962
Abstract
Introduction
Live attenuated influenza vaccines (LAIVs) are being developed to protect humans against future epidemics and pandemics. This study describes the results of a double?blinded randomized placebo?controlled phase I clinical trial of cold?adapted and temperature sensitive H7N3 live attenuated influenza vaccine candidate in healthy seronegative adults.
Objective
The goal of the study was to evaluate the safety, tolerability, immunogenicity and potential shedding and transmission of H7N3 LAIV against H7 avian influenza virus of pandemic potential.
Methods and Findings
Two doses of H7N3 LAIV or placebo were administered to 40 randomly divided subjects (30 received vaccine and 10 placebo). The presence of influenza A virus RNA in nasal swabs was detected in 60.0% and 51.7% of subjects after the first and second vaccination, respectively. In addition, vaccine virus was not detected among placebo recipients demonstrating the absence of person?to?person transmission. The H7N3 live attenuated influenza vaccine demonstrated a good safety profile and was well tolerated. The two?dose immunization resulted in measurable serum and local antibody production and in generation of antigen?specific CD4<SUP>+</SUP> and CD8<SUP>+</SUP> memory T cells. Composite analysis of the immune response which included hemagglutinin inhibition assay, microneutralization tests, and measures of IgG and IgA and virus?specific T cells showed that the majority (86.2%) of vaccine recipients developed serum and/or local antibodies responses and generated CD4<SUP>+</SUP> and CD8<SUP>+</SUP> memory T cells.
Conclusions
The H7N3 LAIV was safe and well tolerated, immunogenic in healthy seronegative adults and elicited production of antibodies broadly reactive against the newly emerged H7N9 avian influenza virus.
Trial registration
ClinicalTrials.gov NCT01511419
_____
Citation: Rudenko L, Kiseleva I, Naykhin AN, Erofeeva M, Stukova M, et al. (2014) Assessment of Human Immune Responses to H7 Avian Influenza Virus of Pandemic Potential: Results from a Placebo?Controlled, Randomized Double?Blind Phase I Study of Live Attenuated H7N3 Influenza Vaccine. PLoS ONE 9(2): e87962. doi:10.1371/journal.pone.0087962
Editor: Ernesto T. A. Marques, University of Pittsburgh, United States of America
Received: October 5, 2013; Accepted: December 24, 2013; Published: February 12, 2014
Copyright: ? 2014 Rudenko 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.
Funding: The study was supported by Program for Appropriate Technologies in Health (PATH) (http://sites.path.org/vaccinedevelopment/influenza/). Some funders (VT, JCV, KN, JF) participated in designing the experiments and critically reviewed the manuscript.
Competing interests: The authors have declared that no competing interests exist.
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