Browsing by Author "Pawinee Jarujareet"

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    Late boosting of the RV144 regimen with AIDSVAX B/E and ALVAC-HIV in HIV-uninfected Thai volunteers: a double-blind, randomised controlled trial
    (2020-04-01) Punnee Pitisuttithum; Sorachai Nitayaphan; Suwat Chariyalertsak; Jaranit Kaewkungwal; Peter Dawson; Jittima Dhitavat; Benjaluck Phonrat; Siriwat Akapirat; Nicos Karasavvas; Lindsay Wieczorek; Victoria Polonis; Michael A. Eller; Poonam Pegu; Dohoon Kim; Alexandra Schuetz; Surat Jongrakthaitae; Yingjun Zhou; Faruk Sinangil; Sanjay Phogat; Carlos A. Diazgranados; James Tartaglia; Elizabeth Heger; Kirsten Smith; Nelson L. Michael; Jean Louis Excler; Merlin L. Robb; Jerome H. Kim; Robert J. O'Connell; Sandhya Vasan; Arom Pitisuthitham; Yupa Sabmee; Narongrid Sirisopana; Chirapa Eamsila; Prapaporn Savaraj; Wanlaya Labwech; Siriluck Teerachia; Nuntisa Chotirosniramit; Taweewat Supindham; Boonlure Pruenglampoo; Patcharaphan Sugandhavesa; Natthapol Kosashunhanan; Oranitcha Kaewthip; Piyathida Sroysuwan; Pawinee Jarujareet; Silvia Ratto-Kim; Sebastian Molnar; Jesse Schoen; Nampueng Churikanont; Saowanit Getchalarat; Nongluck Sangnoi; Bessara Nuntapinit; Anant Phramtong; Pornsuk V. Grandin; Sirinan Madnote; Surawach Rittiroongrad; Boot Kaewboon; Rapee Trichavaroj; Jiraporn Puangkaew; Somsak Chantakulkij; Phiromrat Rakyat; Pornchanok Panjapornsuk; Nipattra Tragonlugsana; Weerawan Chuenarom; Mark de Souza; Viseth Ngauy; Nittaya Phanuphak; Nitiya Chomchey; Puttachard Saengtawan; Nipat Teeratakulpisarn; Rungsun Rerknimitr; Eugene Kroon; Carter A. Lee; Suchada Chinaworapong; GlaxoSmithKline SpA; International Vaccine Institute, Seoul; Sanofi Pasteur SA; The EMMES Corporation; Armed Forces Research Institute of Medical Sciences, Thailand; HJF; Walter Reed Army Institute of Research; Mahidol University; Chiang Mai University; US Army Medical Materiel Development Activity; Global Solutions for Infectious Diseases
    © 2020 Elsevier Ltd Background: The RV144 phase 3 vaccine trial in Thailand demonstrated that ALVAC-HIV (vCP1521) and AIDSVAX B/E administration over 6 months resulted in a 31% efficacy in preventing HIV acquisition. In this trial, we assessed the immunological effect of an additional vaccine boost to the RV144 regimen at varying intervals between the priming vaccine series and the boost. Methods: RV306 is a double-blind, placebo-controlled, randomised clinical trial done at three clinical sites in Thailand. Eligible volunteers were HIV-uninfected individuals aged 20–40 years who were at low risk for HIV infection and in good health. A randomisation schedule was centrally generated with fixed sized strata for Research Institute for Health Sciences Chiang Mai and combined Bangkok clinics. Participants were randomly assigned to one of five groups and then further randomly assigned to either vaccine or placebo. All participants received the primary RV144 vaccine series at months 0, 1, 3, and 6. Group 1 received no additional boost, group 2 received additional AIDSVAX B/E and ALVAC-HIV (vCP1521) or placebo at month 12, group 3 received AIDSVAX B/E alone or placebo at month 12, group 4a received AIDSVAX B/E and ALVAC-HIV or placebo at month 15, and group 4b received AIDSVAX B/E and ALVAC-HIV or placebo at month 18. Primary outcomes were safety and tolerability of these vaccination regimens and cellular and humoral immune responses compared between the RV144 series alone and regimens with late boosts at different timepoints. Safety and tolerability outcomes were assessed by evaluating local and systemic reactogenicity and adverse events in all participants. This trial is registered at ClinicalTrials.gov (NCT01931358); clinical follow-up is now complete. Findings: Between Oct 28, 2013, and April 29, 2014, 367 participants were enrolled, of whom 27 were assigned active vaccination in group 1, 102 in group 2, 101 in group 3, 52 in group 4a, 51 in group 4b, and 34 combined placebo across all the groups. No vaccine-related serious adverse events were recorded. Occurrence and severity of local and systemic reactogenicity were similar across active groups. Groups with late boosts (groups 2, 3, 4a, and 4b) had increased peak plasma IgG-binding antibody levels against gp70 V1V2 relative to group 1 vaccine recipients with no late boost (gp70 V1V2 92TH023 adjusted p<0·02 for each; gp70 V1V2 CaseA2 adjusted p<0·0001 for each). Boosting at month 12 (groups 2 and 3) did not increase gp120 responses compared with the peak responses after the RV144 priming regimen at month 6; however, boosting at month 15 (group 4a) improved responses to gp120 A244gD– D11 (p=0·0003), and boosting at month 18 (group 4b) improved responses to both gp120 A244gD– D11 (p<0·0001) and gp120 MNgD– D11 (p=0·0016). Plasma IgG responses were significantly lower among vaccine recipients boosted at month 12 (pooled groups 2 + 3) than at month 15 (group 4a; adjusted p<0·0001 for each, except for gp70 V1V2 CaseA2, p=0·0142) and at month 18 (group 4b; all adjusted p<0·001). Boosting at month 18 versus month 15 resulted in a significantly higher plasma IgG response to gp120 antigens (all adjusted p<0·01) but not gp70 V1V2 antigens. CD4 functionality and polyfunctionality scores after stimulation with HIV-1 Env peptides (92TH023) increased with delayed boosting. Groups with late boosts had increased functionality and polyfunctionality scores relative to vaccine recipients with no late boost (all adjusted p<0·05, except for the polyfunctionality score in group 1 vs group 4b, p<0·01). Interpretation: Taken together, these results suggest that additional boosting of the RV144 regimen with longer intervals between the primary vaccination series and late boost improved immune responses and might improve the efficacy of preventing HIV acquisition. Funding: US National Institute of Allergy and Infectious Diseases and US Department of the Army.
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    The Thai phase III trial (RV144) vaccine regimen induces T cell responses that preferentially target epitopes within the V2 region of HIV-1 envelope
    (2012-05-15) Mark S. De Souza; Silvia Ratto-Kim; Weerawan Chuenarom; Alexandra Schuetz; Somsak Chantakulkij; Bessara Nuntapinit; Anais Valencia-Micolta; Doris Thelian; Sorachai Nitayaphan; Punnee Pitisuttithum; Robert M. Paris; Jaranit Kaewkungwal; Nelson L. Michael; Supachai Rerks-Ngarm; Bonnie Mathieson; Mary Marovich; Jeffrey R. Currier; Jerome H. Kim; Supamit Chunsuttiwat; Nakorn Premsri; Chawetsan Namwat; Prayura Kunasol; Prasert Thongcharoen; Chirasak Khamboonruang; Valai Bussaratid; Wirach Maek-a-nantawat; Jittima Dhitavat; Pravan Suntharasamai; Swangjai Pungpak; Siriwan Vanijanonta; Jaranit Kaewkunwal; Amnat Khamsiriwatchara; Pawinee Jarujareet; Chirapa Easmila; Suchana Tabprasit; Viseth Ngauy; Robert Paris; Michael Benenson; Patricia Morgan; Arthur Brown; Mark De Souza; Rapee Trichavaroj; Nusara Thaitawat; Kanyasiri Kongnonkok; Boot Keawboon; Yuwadee Phuang-Ngern; Susan Mason; Sanjay Gurunathan; Jim Tartaglia; John G. McNeil; Robin Harkness; Claude Meric; Lynn Baglyos; Raphaelle El Habib; Don Francis; Carter Lee; Elizabeth Adams; Merlin L. Robb; Mark Milazzo; Amy Bolen; Beryl Wessner; Jeffrey Currier; Deborah L. Birx; Don Stablein; Terry Germanson; Len Dally; Jean Louis Excler; Jeffrey Berenberg; Armed Forces Research Institute of Medical Sciences, Thailand; Walter Reed Army Institute of Research; Mahidol University; Thailand Ministry of Public Health; National Institutes of Health, Bethesda; Sanofi Pasteur; Sanofi Pasteur; Global Solutions in Infectious Diseases; National Institute of Allergy and Infectious Diseases; U.S. Army Medical Research and Materiel Command; Centers for Disease Control and Prevention; The EMMES Corporation; International AIDS Vaccine Initiative; Tripler Regional Med Center
    The Thai HIV phase III prime/boost vaccine trial (RV144) using ALVAC-HIV (vCP1521) and AIDSVAX B/E was, to our knowledge, the first to demonstrate acquisition efficacy. Vaccine-induced, cell-mediated immune responses were assessed. T cell epitope mapping studies using IFN-γ ELISPOT was performed on PBMCs from HIV-1-uninfected vaccine (n = 61) and placebo (n = 10) recipients using HIV-1 Env peptides. Positive responses were measured in 25 (41%) vaccinees and were predominantly CD4 + T cell-mediated. Responses were targeted within the HIV Env region, with 15 of 25 (60%) of vaccinees recognizing peptides derived from the V2 region of HIV-1 Env, which includes the α 4 β 7 integrin binding site. Intracellular cytokine staining confirmed that Env responses predominated (19 of 30; 63% of vaccine recipients) and were mediated by polyfunctional effector memory CD4 + T cells, with the majority of responders producing both IL-2 and IFN-γ (12 of 19; 63%). HIV Env Ab titers were higher in subjects with IL-2 compared with those without IL-2-secreting HIV Env-specific effector memory T cells. Proliferation assays revealed that HIV Ag-specific T cells were CD4 + , with the majority (80%) expressing CD107a. HIV-specific T cell lines obtained from vaccine recipients confirmed V2 specificity, polyfunctionality, and functional cytolytic capacity. Although the RV144 T cell responses were modest in frequency compared with humoral immune responses, the CD4 + T cell response was directed to HIV-1 Env and more particularly the V2 region.