Giuseppe
Emeritus
[Source: The Journal of Infectious Diseases, full page: (LINK). Abstract, edited.]
A live attenuated H5N1 vaccine induces long-term immunity in the absence of a primary antibody response
Kawsar R. Talaat 1,*, Catherine J. Luke 2,*, Surender Khurana 3, Jody Manischewitz 3, Lisa R. King 3, Bridget A. McMahon 1,#, Ruth A. Karron 1, Kristen Lewis 4, Jing Qin 5, Dean Follmann 5, Hana Golding 3, Kathleen Neuzil 4 and Kanta Subbarao 2
Author Affiliations: <SUP>1</SUP>Center For Immunization Research, Johns Hopkins Bloomberg School of Public Health, 624 North Broadway, Baltimore, MD 21205, USA <SUP>2</SUP>Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA <SUP>3</SUP>Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Bethesda, MD 20892, USA <SUP>4</SUP>PATH, PO Box 900922, Seattle, WA 98109, USA <SUP>5</SUP>Biostatistics Research Branch National Institute of Allergy and Infectious Diseases, National Institutes of Health, 6700B Rockledge Drive, Bethesda, MD 20892, USA
Corresponding Author: Dr. Kanta Subbarao, Laboratory of Infectious Diseases, NIAID, NIH, 33 North Drive, MSC 3203, Bethesda, MD 20892-3203, USA, Tel. (301) 451 3839, ksubbarao@niaid.nih.gov
* K.T. and C.L. contributed equally to this work
# B.A.M. is now at SNBL Clinical Pharmacology Center, Inc.
<CITE><ABBR>J Infect Dis.</ABBR> (2014) doi: 10.1093/infdis/jiu123 </CITE>First published online: March 5, 2014
Abstract
Background.
Highly pathogenic avian influenza H5N1 viruses cause severe infections in humans. We generated two H5N1 pandemic (p) live attenuated influenza vaccines (LAIV) but they failed to elicit a primary immune response. Our objective was to determine whether the vaccines primed or established long lasting immunity that could be detected by administration of inactivated H5N1 influenza vaccine (ISIV).
Methods.
The following groups were invited to participate in the study: persons who previously received H5N1 pLAIV; persons who previously received an irrelevant H7N3 pLAIV, and H5N1- and LAIV-na?ve community members. LAIV experienced subjects received a single 45 ?g dose of H5N1 ISIV. H5N1-and LAIV-na?ve subjects received either one or two doses of ISIV.
Results.
In subjects who had previously received antigenically matched H5N1 pLAIV followed by one dose of ISIV compared with H5N1-and LAIV-na?ve two dose ISIV recipients, we observed an increased frequency (82% vs. 50%) and significantly higher titer (112 vs. 76) hemagglutination inhibition antibody response (p=0?04). The affinity of antibody and breadth of cross-clade neutralization was also enhanced in H5N1 pLAIV-primed subjects.
Conclusions.
ISIV administration unmasked long lasting immunity in H5N1 pLAIV recipients with a rapid, high titer, high quality antibody response that was broadly cross-reactive across several H5N1 clades.
Clinicaltrials gov number. NCT01109329
Received October 17, 2013. Revision received January 17, 2014. Accepted January 23, 2014.
Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.
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A live attenuated H5N1 vaccine induces long-term immunity in the absence of a primary antibody response
Kawsar R. Talaat 1,*, Catherine J. Luke 2,*, Surender Khurana 3, Jody Manischewitz 3, Lisa R. King 3, Bridget A. McMahon 1,#, Ruth A. Karron 1, Kristen Lewis 4, Jing Qin 5, Dean Follmann 5, Hana Golding 3, Kathleen Neuzil 4 and Kanta Subbarao 2
Author Affiliations: <SUP>1</SUP>Center For Immunization Research, Johns Hopkins Bloomberg School of Public Health, 624 North Broadway, Baltimore, MD 21205, USA <SUP>2</SUP>Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA <SUP>3</SUP>Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Bethesda, MD 20892, USA <SUP>4</SUP>PATH, PO Box 900922, Seattle, WA 98109, USA <SUP>5</SUP>Biostatistics Research Branch National Institute of Allergy and Infectious Diseases, National Institutes of Health, 6700B Rockledge Drive, Bethesda, MD 20892, USA
Corresponding Author: Dr. Kanta Subbarao, Laboratory of Infectious Diseases, NIAID, NIH, 33 North Drive, MSC 3203, Bethesda, MD 20892-3203, USA, Tel. (301) 451 3839, ksubbarao@niaid.nih.gov
* K.T. and C.L. contributed equally to this work
# B.A.M. is now at SNBL Clinical Pharmacology Center, Inc.
<CITE><ABBR>J Infect Dis.</ABBR> (2014) doi: 10.1093/infdis/jiu123 </CITE>First published online: March 5, 2014
Abstract
Background.
Highly pathogenic avian influenza H5N1 viruses cause severe infections in humans. We generated two H5N1 pandemic (p) live attenuated influenza vaccines (LAIV) but they failed to elicit a primary immune response. Our objective was to determine whether the vaccines primed or established long lasting immunity that could be detected by administration of inactivated H5N1 influenza vaccine (ISIV).
Methods.
The following groups were invited to participate in the study: persons who previously received H5N1 pLAIV; persons who previously received an irrelevant H7N3 pLAIV, and H5N1- and LAIV-na?ve community members. LAIV experienced subjects received a single 45 ?g dose of H5N1 ISIV. H5N1-and LAIV-na?ve subjects received either one or two doses of ISIV.
Results.
In subjects who had previously received antigenically matched H5N1 pLAIV followed by one dose of ISIV compared with H5N1-and LAIV-na?ve two dose ISIV recipients, we observed an increased frequency (82% vs. 50%) and significantly higher titer (112 vs. 76) hemagglutination inhibition antibody response (p=0?04). The affinity of antibody and breadth of cross-clade neutralization was also enhanced in H5N1 pLAIV-primed subjects.
Conclusions.
ISIV administration unmasked long lasting immunity in H5N1 pLAIV recipients with a rapid, high titer, high quality antibody response that was broadly cross-reactive across several H5N1 clades.
Clinicaltrials gov number. NCT01109329
Received October 17, 2013. Revision received January 17, 2014. Accepted January 23, 2014.
Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.
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