Publication:
Late boosting of the RV144 regimen with AIDSVAX B/E and ALVAC-HIV in HIV-uninfected Thai volunteers: a double-blind, randomised controlled trial

Issued Date

2020-04-01

Resource Type

Article

File Type

video/youtube

ISSN

23523018

DOI

10.1016/S2352-3018(19)30406-0

Other identifier(s)

2-s2.0-85079586810

Rights

Mahidol University

Rights Holder(s)

SCOPUS

Bibliographic Citation

The Lancet HIV. Vol.7, No.4 (2020), e238-e248

Suggested Citation

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 Late boosting of the RV144 regimen with AIDSVAX B/E and ALVAC-HIV in HIV-uninfected Thai volunteers: a double-blind, randomised controlled trial. The Lancet HIV. Vol.7, No.4 (2020), e238-e248. doi:10.1016/S2352-3018(19)30406-0 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/54573

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Title

Late boosting of the RV144 regimen with AIDSVAX B/E and ALVAC-HIV in HIV-uninfected Thai volunteers: a double-blind, randomised controlled trial

Author(s)

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

Other Contributor(s)

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

Abstract

© 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.

Keyword(s)

Immunology and Microbiology
 Medicine

Availability

URI

https://repository.li.mahidol.ac.th/handle/20.500.14594/54573

Collections

Scopus 2020