Please use this identifier to cite or link to this item:
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
Authors: 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
Keywords: Immunology and Microbiology
Issue Date: 1-Apr-2020
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 (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.
ISSN: 23523018
Appears in Collections:CMUL: Journal Articles

Files in This Item:
There are no files associated with this item.

Items in CMUIR are protected by copyright, with all rights reserved, unless otherwise indicated.