An open label Phase I trial of a live attenuated H6N1 influenza virus vaccine in healthy adults

Kawsar R. Talaat; Ruth A. Karron; Catherine J. Luke; Bhagvanji Thumar; Bridget A. McMahon; Grace L. Chen; Elaine W. Lamirande; Hong Jin; Kathy L. Coelingh; George Kemble; Kanta Subbarao

doi:10.1016/j.vaccine.2011.02.043

An open label Phase I trial of a live attenuated H6N1 influenza virus vaccine in healthy adults

Kawsar R. Talaat, Ruth A. Karron, Catherine J. Luke, Bhagvanji Thumar, Bridget A. McMahon, Grace L. Chen, Elaine W. Lamirande, Hong Jin, Kathy L. Coelingh, George Kemble, Kanta Subbarao

Bloomberg School of Public Health

Research output: Contribution to journal › Article › peer-review

32 Scopus citations

Abstract

Background: We describe the results of an open label Phase I trial of a live attenuated H6N1 influenza virus vaccine (ClinicalTrials.gov Identifier: NCT00734175). Methods and findings: We evaluated the safety, infectivity, and immunogenicity of two doses of 10⁷ TCID₅₀ of the H6N1 Teal HK 97/AA ca vaccine, a cold-adapted and temperature sensitive live, attenuated influenza vaccine (LAIV) in healthy seronegative adults.Twenty-two participants received the first dose of the vaccine, and 18 received the second dose of vaccine 4 weeks later. The vaccine had a safety profile similar to that of other investigational LAIVs bearing avian hemagglutinin (HA) and neuraminidase (NA) genes. The vaccine was highly restricted in replication: two participants had virus detectable by rRT-PCR beyond day 1 after each dose. Antibody responses to the vaccine were also restricted: 43% of participants developed a serum antibody response as measured by any assay: 5% by hemagglutination-inhibition assay, 5% by microneutralization assay, 29% by ELISA for H6 HA-specific IgG and 24% by ELISA for H6 HA specific IgA after either 1 or 2 doses. Following the second dose, vaccine specific IgG and IgA secreting cells as measured by ELISPOT increased from a mean of 0.6 to 9.2/10⁶ PBMCs and from 0.2 to 2.2/10⁶ PBMCs, respectively. Conclusion: The H6N1 LAIV had a safety profile similar to that of LAIV bearing other HA and NA genes, but was highly restricted in replication in healthy seronegative adults. The H6N1 LAIV was also not as immunogenic as the seasonal LAIV.

Original language	English (US)
Pages (from-to)	3144-3148
Number of pages	5
Journal	Vaccine
Volume	29
Issue number	17
DOIs	https://doi.org/10.1016/j.vaccine.2011.02.043
State	Published - Apr 12 2011

Keywords

Avian influenza
H6N1
Live attenuated
Vaccine

ASJC Scopus subject areas

Molecular Medicine
General Immunology and Microbiology
General Veterinary
Public Health, Environmental and Occupational Health
Infectious Diseases

Access to Document

10.1016/j.vaccine.2011.02.043

Cite this

@article{6c8f99bb451a4550ba3abbc9734005ae,

title = "An open label Phase I trial of a live attenuated H6N1 influenza virus vaccine in healthy adults",

abstract = "Background: We describe the results of an open label Phase I trial of a live attenuated H6N1 influenza virus vaccine (ClinicalTrials.gov Identifier: NCT00734175). Methods and findings: We evaluated the safety, infectivity, and immunogenicity of two doses of 107 TCID50 of the H6N1 Teal HK 97/AA ca vaccine, a cold-adapted and temperature sensitive live, attenuated influenza vaccine (LAIV) in healthy seronegative adults.Twenty-two participants received the first dose of the vaccine, and 18 received the second dose of vaccine 4 weeks later. The vaccine had a safety profile similar to that of other investigational LAIVs bearing avian hemagglutinin (HA) and neuraminidase (NA) genes. The vaccine was highly restricted in replication: two participants had virus detectable by rRT-PCR beyond day 1 after each dose. Antibody responses to the vaccine were also restricted: 43% of participants developed a serum antibody response as measured by any assay: 5% by hemagglutination-inhibition assay, 5% by microneutralization assay, 29% by ELISA for H6 HA-specific IgG and 24% by ELISA for H6 HA specific IgA after either 1 or 2 doses. Following the second dose, vaccine specific IgG and IgA secreting cells as measured by ELISPOT increased from a mean of 0.6 to 9.2/106 PBMCs and from 0.2 to 2.2/106 PBMCs, respectively. Conclusion: The H6N1 LAIV had a safety profile similar to that of LAIV bearing other HA and NA genes, but was highly restricted in replication in healthy seronegative adults. The H6N1 LAIV was also not as immunogenic as the seasonal LAIV.",

keywords = "Avian influenza, H6N1, Live attenuated, Vaccine",

author = "Talaat, {Kawsar R.} and Karron, {Ruth A.} and Luke, {Catherine J.} and Bhagvanji Thumar and McMahon, {Bridget A.} and Chen, {Grace L.} and Lamirande, {Elaine W.} and Hong Jin and Coelingh, {Kathy L.} and George Kemble and Kanta Subbarao",

note = "Funding Information: We wish to thank Ruval Comendador, Jasmine Jennings and Paula Williams-Soro for expert clinical assistance, Susan DiLorenzo and Nicole Yoder for expert technical assistance. We would also like to thank Zhongying Chen, Weidong Cui, Kathy Wang, Silas Nwagwu, Alfred Pan, Lynne Fitch, Patricia Ryan, So-Ching Brazer, David Prichett, and Edith Matsuyama of MedImmune for vaccine manufacturing and testing. This research was supported by the Intramural Research Program of the NIAID, NIH. This research was performed as a Cooperative Research and Development Agreement (CRADA) (CRADA No: AI-0155) between the Laboratory of Infectious Diseases, NIAID and MedImmune. ",

year = "2011",

month = apr,

day = "12",

doi = "10.1016/j.vaccine.2011.02.043",

language = "English (US)",

volume = "29",

pages = "3144--3148",

journal = "Vaccine",

issn = "0264-410X",

publisher = "Elsevier BV",

number = "17",

}

TY - JOUR

T1 - An open label Phase I trial of a live attenuated H6N1 influenza virus vaccine in healthy adults

AU - Talaat, Kawsar R.

AU - Karron, Ruth A.

AU - Luke, Catherine J.

AU - Thumar, Bhagvanji

AU - McMahon, Bridget A.

AU - Chen, Grace L.

AU - Lamirande, Elaine W.

AU - Jin, Hong

AU - Coelingh, Kathy L.

AU - Kemble, George

AU - Subbarao, Kanta

N1 - Funding Information: We wish to thank Ruval Comendador, Jasmine Jennings and Paula Williams-Soro for expert clinical assistance, Susan DiLorenzo and Nicole Yoder for expert technical assistance. We would also like to thank Zhongying Chen, Weidong Cui, Kathy Wang, Silas Nwagwu, Alfred Pan, Lynne Fitch, Patricia Ryan, So-Ching Brazer, David Prichett, and Edith Matsuyama of MedImmune for vaccine manufacturing and testing. This research was supported by the Intramural Research Program of the NIAID, NIH. This research was performed as a Cooperative Research and Development Agreement (CRADA) (CRADA No: AI-0155) between the Laboratory of Infectious Diseases, NIAID and MedImmune.

PY - 2011/4/12

Y1 - 2011/4/12

N2 - Background: We describe the results of an open label Phase I trial of a live attenuated H6N1 influenza virus vaccine (ClinicalTrials.gov Identifier: NCT00734175). Methods and findings: We evaluated the safety, infectivity, and immunogenicity of two doses of 107 TCID50 of the H6N1 Teal HK 97/AA ca vaccine, a cold-adapted and temperature sensitive live, attenuated influenza vaccine (LAIV) in healthy seronegative adults.Twenty-two participants received the first dose of the vaccine, and 18 received the second dose of vaccine 4 weeks later. The vaccine had a safety profile similar to that of other investigational LAIVs bearing avian hemagglutinin (HA) and neuraminidase (NA) genes. The vaccine was highly restricted in replication: two participants had virus detectable by rRT-PCR beyond day 1 after each dose. Antibody responses to the vaccine were also restricted: 43% of participants developed a serum antibody response as measured by any assay: 5% by hemagglutination-inhibition assay, 5% by microneutralization assay, 29% by ELISA for H6 HA-specific IgG and 24% by ELISA for H6 HA specific IgA after either 1 or 2 doses. Following the second dose, vaccine specific IgG and IgA secreting cells as measured by ELISPOT increased from a mean of 0.6 to 9.2/106 PBMCs and from 0.2 to 2.2/106 PBMCs, respectively. Conclusion: The H6N1 LAIV had a safety profile similar to that of LAIV bearing other HA and NA genes, but was highly restricted in replication in healthy seronegative adults. The H6N1 LAIV was also not as immunogenic as the seasonal LAIV.

AB - Background: We describe the results of an open label Phase I trial of a live attenuated H6N1 influenza virus vaccine (ClinicalTrials.gov Identifier: NCT00734175). Methods and findings: We evaluated the safety, infectivity, and immunogenicity of two doses of 107 TCID50 of the H6N1 Teal HK 97/AA ca vaccine, a cold-adapted and temperature sensitive live, attenuated influenza vaccine (LAIV) in healthy seronegative adults.Twenty-two participants received the first dose of the vaccine, and 18 received the second dose of vaccine 4 weeks later. The vaccine had a safety profile similar to that of other investigational LAIVs bearing avian hemagglutinin (HA) and neuraminidase (NA) genes. The vaccine was highly restricted in replication: two participants had virus detectable by rRT-PCR beyond day 1 after each dose. Antibody responses to the vaccine were also restricted: 43% of participants developed a serum antibody response as measured by any assay: 5% by hemagglutination-inhibition assay, 5% by microneutralization assay, 29% by ELISA for H6 HA-specific IgG and 24% by ELISA for H6 HA specific IgA after either 1 or 2 doses. Following the second dose, vaccine specific IgG and IgA secreting cells as measured by ELISPOT increased from a mean of 0.6 to 9.2/106 PBMCs and from 0.2 to 2.2/106 PBMCs, respectively. Conclusion: The H6N1 LAIV had a safety profile similar to that of LAIV bearing other HA and NA genes, but was highly restricted in replication in healthy seronegative adults. The H6N1 LAIV was also not as immunogenic as the seasonal LAIV.

KW - Avian influenza

KW - H6N1

KW - Live attenuated

KW - Vaccine

UR - http://www.scopus.com/inward/record.url?scp=79954611107&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79954611107&partnerID=8YFLogxK

U2 - 10.1016/j.vaccine.2011.02.043

DO - 10.1016/j.vaccine.2011.02.043

M3 - Article

C2 - 21377509

AN - SCOPUS:79954611107

SN - 0264-410X

VL - 29

SP - 3144

EP - 3148

JO - Vaccine

JF - Vaccine

IS - 17

ER -

An open label Phase I trial of a live attenuated H6N1 influenza virus vaccine in healthy adults

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this