Giuseppe
Emeritus
[Source: PLoS ONE, full text: (LINK). Abstract, edited.]
Safety and Reactogenicity of Canarypox ALVAC-HIV (vCP1521) and HIV-1 gp120 AIDSVAX B/E Vaccination in an Efficacy Trial in Thailand
Punnee Pitisuttithum<SUP>1</SUP><SUP>*</SUP>, Supachai Rerks-Ngarm<SUP>2</SUP>, Valai Bussaratid<SUP>1</SUP>, Jittima Dhitavat<SUP>1</SUP>, Wirach Maekanantawat<SUP>1</SUP>, Swangjai Pungpak<SUP>1</SUP>, Pravan Suntharasamai<SUP>1</SUP>, Sirivan Vanijanonta<SUP>1</SUP>, Sorachai Nitayapan<SUP>3</SUP>, Jaranit Kaewkungwal<SUP>1</SUP>, Michael Benenson<SUP>3</SUP>, Patricia Morgan<SUP>3</SUP>, Robert J. O'Connell<SUP>4</SUP>, Jeffrey Berenberg<SUP>5</SUP>, Sanjay Gurunathan<SUP>6</SUP>, Donald P. Francis<SUP>7</SUP>, Robert Paris<SUP>8</SUP>, Joseph Chiu<SUP>9</SUP>, Donald Stablein<SUP>10</SUP>, Nelson L. Michael<SUP>4</SUP>, Jean-Louis Excler<SUP>4</SUP>, Merlin L. Robb<SUP>4</SUP>, Jerome H. Kim<SUP>4</SUP>
1 Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand, 2 Department of Disease Control, Ministry of Public Health, Bangkok, Thailand, 3 Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand, 4 U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Rockville, Maryland, United States of America, 5 Department of Medicine, Tripler Army Medical Center, Honolulu, Hawaii, United States of America, 6 Sanofi Pasteur, Swiftwater, Pennsylvania, United States of America, 7 Global Solutions for Infectious Diseases, South San Francisco, California, United States of America, 8 Walter Reed Army Medical Center, Washington, D. C., United States of America, 9 Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America, 10 EMMES Corporation, Rockville, Maryland, United States of America
Abstract
Background
A prime-boost vaccination regimen with ALVAC-HIV (vCP1521) administered intramuscularly at 0, 4, 12, and 24 weeks and gp120 AIDSVAX B/E at 12 and 24 weeks demonstrated modest efficacy of 31.2% for prevention of HIV acquisition in HIV-uninfected adults participating in a community-based efficacy trial in Thailand.
Methodology/Principal Findings
Reactogenicity was recorded for 3 days following vaccination. Adverse events were monitored every 6 months for 3.5 years, during which pregnancy outcomes were recorded. Of the 16,402 volunteers, 69% of the participants reported an adverse event any time after the first dose. Only 32.9% experienced an AE within 30 days following any vaccination. Overall adverse event rates and attribution of relatedness did not differ between groups. The frequency of serious adverse events was similar in vaccine (14.3%) and placebo (14.9%) recipients (p = 0.33). None of the 160 deaths (85 in vaccine and 75 in placebo recipients, p = 0.43) was assessed as related to vaccine. The most common cause of death was trauma or traffic accident. Approximately 30% of female participants reported a pregnancy during the study. Abnormal pregnancy outcomes were experienced in 17.1% of vaccine and 14.6% (p = 0.13) of placebo recipients. When the conception occurred within 3 months (estimated) of a vaccination, the majority of these abnormal outcomes were spontaneous or elective abortions among 22.2% and 15.3% of vaccine and placebo pregnant recipients, respectively (p = 0.08). Local reactions occurred in 88.0% of vaccine and 61.0% of placebo recipients (p<0.001) and were more frequent after ALVAC-HIV than AIDSVAX B/E vaccination. Systemic reactions were more frequent in vaccine than placebo recipients (77.2% vs. 59.8%, p<0.001). Local and systemic reactions were mostly mild to moderate, resolving within 3 days.
Conclusions/Significance
The ALVAC-HIV and AIDSVAX B/E vaccine regimen was found to be safe, well tolerated and suitable for potential large-scale use in Thailand.
Trial Registration
ClinicalTrials.gov NCT00223080
Citation: Pitisuttithum P, Rerks-Ngarm S, Bussaratid V, Dhitavat J, Maekanantawat W, et al. (2011) Safety and Reactogenicity of Canarypox ALVAC-HIV (vCP1521) and HIV-1 gp120 AIDSVAX B/E Vaccination in an Efficacy Trial in Thailand. PLoS ONE 6(12): e27837. doi:10.1371/journal.pone.0027837
Editor: Esper Georges Kallas, University of Sao Paulo, Brazil
Received: June 22, 2011; Accepted: October 26, 2011; Published: December 21, 2011
Copyright: ? 2011 Pitisuttithum 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: Supported in part by an Interagency Agreement (Y1-AI-2642-12) between the U.S. Army Medical Research and Materiel Command and the National Institute of Allergy and Infectious Diseases and by a cooperative agreement (W81XWH-07-2-0067) between the Henry M. Jackson Foundation for the Advancement of Military Medicine and the U.S. Department of Defense. The U.S. Army was also involved in the planning, funding, execution and analysis of the trial; it was involved in both the preparation of the manuscript and the decision to publish. NIAID was involved in the planning and funding. Sanofi Pasteur provided the ALVAC-HIV vaccine, and Global Solutions for Infectious Diseases (VaxGen) provided the reagents for the immunogenicity assays. The manufacturers were full trial collaborators and were a part of the phase 3 trial steering committee.
Competing interests: Sanjay Gurunathan reports being employee of Sanofi Pasteur, who provided the reagents for the ALVAC-HIV vaccine. Donald P. Francis is employee of Global Solutions for Infectious Diseases (VaxGen), who provided the reagents for the immunogenicity assays. No other potential conflict of interest relevant to this article was reported. The views expressed are those of the authors and should not be construed to represent the positions of the U.S. Army or Department of Defense or other institutions involved in the study. Donald Stablein is employee of The EMMES Corporation, a Contract Research Organization (CRO), responsible for the statistical analysis of the clinical trial data. This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials.
* E-mail: tmppt@mahidol.ac.th
- ------Punnee Pitisuttithum<SUP>1</SUP><SUP>*</SUP>, Supachai Rerks-Ngarm<SUP>2</SUP>, Valai Bussaratid<SUP>1</SUP>, Jittima Dhitavat<SUP>1</SUP>, Wirach Maekanantawat<SUP>1</SUP>, Swangjai Pungpak<SUP>1</SUP>, Pravan Suntharasamai<SUP>1</SUP>, Sirivan Vanijanonta<SUP>1</SUP>, Sorachai Nitayapan<SUP>3</SUP>, Jaranit Kaewkungwal<SUP>1</SUP>, Michael Benenson<SUP>3</SUP>, Patricia Morgan<SUP>3</SUP>, Robert J. O'Connell<SUP>4</SUP>, Jeffrey Berenberg<SUP>5</SUP>, Sanjay Gurunathan<SUP>6</SUP>, Donald P. Francis<SUP>7</SUP>, Robert Paris<SUP>8</SUP>, Joseph Chiu<SUP>9</SUP>, Donald Stablein<SUP>10</SUP>, Nelson L. Michael<SUP>4</SUP>, Jean-Louis Excler<SUP>4</SUP>, Merlin L. Robb<SUP>4</SUP>, Jerome H. Kim<SUP>4</SUP>
1 Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand, 2 Department of Disease Control, Ministry of Public Health, Bangkok, Thailand, 3 Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand, 4 U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Rockville, Maryland, United States of America, 5 Department of Medicine, Tripler Army Medical Center, Honolulu, Hawaii, United States of America, 6 Sanofi Pasteur, Swiftwater, Pennsylvania, United States of America, 7 Global Solutions for Infectious Diseases, South San Francisco, California, United States of America, 8 Walter Reed Army Medical Center, Washington, D. C., United States of America, 9 Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America, 10 EMMES Corporation, Rockville, Maryland, United States of America
Abstract
Background
A prime-boost vaccination regimen with ALVAC-HIV (vCP1521) administered intramuscularly at 0, 4, 12, and 24 weeks and gp120 AIDSVAX B/E at 12 and 24 weeks demonstrated modest efficacy of 31.2% for prevention of HIV acquisition in HIV-uninfected adults participating in a community-based efficacy trial in Thailand.
Methodology/Principal Findings
Reactogenicity was recorded for 3 days following vaccination. Adverse events were monitored every 6 months for 3.5 years, during which pregnancy outcomes were recorded. Of the 16,402 volunteers, 69% of the participants reported an adverse event any time after the first dose. Only 32.9% experienced an AE within 30 days following any vaccination. Overall adverse event rates and attribution of relatedness did not differ between groups. The frequency of serious adverse events was similar in vaccine (14.3%) and placebo (14.9%) recipients (p = 0.33). None of the 160 deaths (85 in vaccine and 75 in placebo recipients, p = 0.43) was assessed as related to vaccine. The most common cause of death was trauma or traffic accident. Approximately 30% of female participants reported a pregnancy during the study. Abnormal pregnancy outcomes were experienced in 17.1% of vaccine and 14.6% (p = 0.13) of placebo recipients. When the conception occurred within 3 months (estimated) of a vaccination, the majority of these abnormal outcomes were spontaneous or elective abortions among 22.2% and 15.3% of vaccine and placebo pregnant recipients, respectively (p = 0.08). Local reactions occurred in 88.0% of vaccine and 61.0% of placebo recipients (p<0.001) and were more frequent after ALVAC-HIV than AIDSVAX B/E vaccination. Systemic reactions were more frequent in vaccine than placebo recipients (77.2% vs. 59.8%, p<0.001). Local and systemic reactions were mostly mild to moderate, resolving within 3 days.
Conclusions/Significance
The ALVAC-HIV and AIDSVAX B/E vaccine regimen was found to be safe, well tolerated and suitable for potential large-scale use in Thailand.
Trial Registration
ClinicalTrials.gov NCT00223080
Citation: Pitisuttithum P, Rerks-Ngarm S, Bussaratid V, Dhitavat J, Maekanantawat W, et al. (2011) Safety and Reactogenicity of Canarypox ALVAC-HIV (vCP1521) and HIV-1 gp120 AIDSVAX B/E Vaccination in an Efficacy Trial in Thailand. PLoS ONE 6(12): e27837. doi:10.1371/journal.pone.0027837
Editor: Esper Georges Kallas, University of Sao Paulo, Brazil
Received: June 22, 2011; Accepted: October 26, 2011; Published: December 21, 2011
Copyright: ? 2011 Pitisuttithum 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: Supported in part by an Interagency Agreement (Y1-AI-2642-12) between the U.S. Army Medical Research and Materiel Command and the National Institute of Allergy and Infectious Diseases and by a cooperative agreement (W81XWH-07-2-0067) between the Henry M. Jackson Foundation for the Advancement of Military Medicine and the U.S. Department of Defense. The U.S. Army was also involved in the planning, funding, execution and analysis of the trial; it was involved in both the preparation of the manuscript and the decision to publish. NIAID was involved in the planning and funding. Sanofi Pasteur provided the ALVAC-HIV vaccine, and Global Solutions for Infectious Diseases (VaxGen) provided the reagents for the immunogenicity assays. The manufacturers were full trial collaborators and were a part of the phase 3 trial steering committee.
Competing interests: Sanjay Gurunathan reports being employee of Sanofi Pasteur, who provided the reagents for the ALVAC-HIV vaccine. Donald P. Francis is employee of Global Solutions for Infectious Diseases (VaxGen), who provided the reagents for the immunogenicity assays. No other potential conflict of interest relevant to this article was reported. The views expressed are those of the authors and should not be construed to represent the positions of the U.S. Army or Department of Defense or other institutions involved in the study. Donald Stablein is employee of The EMMES Corporation, a Contract Research Organization (CRO), responsible for the statistical analysis of the clinical trial data. This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials.
* E-mail: tmppt@mahidol.ac.th