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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. 2014; 9(2):e87962.Plos

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⁺ and CD8⁺ 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⁺ and CD8⁺ 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.

Authors+Show Affiliations

Department of Virology, Institute of Experimental Medicine, Saint Petersburg, Russia.Department of Virology, Institute of Experimental Medicine, Saint Petersburg, Russia.Department of Virology, Institute of Experimental Medicine, Saint Petersburg, Russia.Department of Epidemiology and Prophylaxis, Institute of Influenza, Saint Petersburg, Russia.Department of Molecular Virology, Institute of Influenza, Saint Petersburg, Russia.Department of Virology, Institute of Experimental Medicine, Saint Petersburg, Russia.Department of Virology, Institute of Experimental Medicine, Saint Petersburg, Russia.Department of Molecular Virology, Institute of Influenza, Saint Petersburg, Russia.Department of Biotechnology, Institute of Influenza, Saint Petersburg, Russia.Department of Molecular Virology, Institute of Influenza, Saint Petersburg, Russia.Department of Molecular Virology, Institute of Influenza, Saint Petersburg, Russia.Department of Virology, Institute of Experimental Medicine, Saint Petersburg, Russia.Department of Virology, Institute of Experimental Medicine, Saint Petersburg, Russia.Department of Virology, Institute of Experimental Medicine, Saint Petersburg, Russia.Department of Virology, Institute of Experimental Medicine, Saint Petersburg, Russia.Department of Virology, Institute of Experimental Medicine, Saint Petersburg, Russia.Department of Preclinical Trials, Microgen, Moscow, Russia.Program for Appropriate Technologies in Health, Seattle, Washington, United States of America.Program for Appropriate Technologies in Health, Seattle, Washington, United States of America.Program for Appropriate Technologies in Health, Seattle, Washington, United States of America.Program for Appropriate Technologies in Health, Seattle, Washington, United States of America.Department of Molecular Virology, Institute of Influenza, Saint Petersburg, Russia.

Pub Type(s)

Clinical Trial, Phase I
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24533064

Citation

Rudenko, Larisa, et al. "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, vol. 9, no. 2, 2014, pp. e87962.
Rudenko L, Kiseleva I, Naykhin AN, et al. 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. 2014;9(2):e87962.
Rudenko, L., Kiseleva, I., Naykhin, A. N., Erofeeva, M., Stukova, M., Donina, S., Petukhova, G., Pisareva, M., Krivitskaya, V., Grudinin, M., Buzitskaya, Z., Isakova-Sivak, I., Kuznetsova, S., Larionova, N., Desheva, J., Dubrovina, I., Nikiforova, A., Victor, J. C., Neuzil, K., ... Kiselev, O. (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. https://doi.org/10.1371/journal.pone.0087962
Rudenko L, et al. 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. 2014;9(2):e87962. PubMed PMID: 24533064.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Rudenko,Larisa, AU - Kiseleva,Irina, AU - Naykhin,Anatoly N, AU - Erofeeva,Marianna, AU - Stukova,Marina, AU - Donina,Svetlana, AU - Petukhova,Galina, AU - Pisareva,Maria, AU - Krivitskaya,Vera, AU - Grudinin,Michael, AU - Buzitskaya,Zhanna, AU - Isakova-Sivak,Irina, AU - Kuznetsova,Svetlana, AU - Larionova,Natalie, AU - Desheva,Julia, AU - Dubrovina,Irina, AU - Nikiforova,Alexandra, AU - Victor,John C, AU - Neuzil,Kathy, AU - Flores,Jorge, AU - Tsvetnitsky,Vadim, AU - Kiselev,Oleg, Y1 - 2014/02/12/ PY - 2013/10/05/received PY - 2013/12/24/accepted PY - 2014/2/18/entrez PY - 2014/2/18/pubmed PY - 2015/1/7/medline SP - e87962 EP - e87962 JF - PloS one JO - PLoS One VL - 9 IS - 2 N2 - 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⁺ and CD8⁺ 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⁺ and CD8⁺ 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. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/24533064/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_ L2 - https://dx.plos.org/10.1371/journal.pone.0087962 DB - PRIME DP - Unbound Medicine ER -