Randomized, Double-Blind Evaluation of Late Boost Strategies for HIV-Uninfected Vaccine Recipients in the RV144 HIV Vaccine Efficacy Trial.
The RV144 ALVAC-HIV prime, AIDSVAX B/E boost afforded 60% efficacy against human immunodeficiency virus (HIV) acquisition at 1 year, waning to 31.2% after 3.5 years. We hypothesized that additional vaccinations might augment immune correlates of protection.



In a randomized placebo-controlled double-blind study of 162 HIV-negative RV144 vaccine recipients, we evaluated 2 additional boosts, given 6-8 years since RV144 vaccination, for safety and immunogenicity, at weeks 0 and 24. Study groups 1-3 received ALVAC-HIV+AIDSVAX B/E, AIDSVAX B/E, and ALVAC-HIV, respectively, or placebo.



Vaccines were well tolerated. For groups 1 and 2, plasma immunoglobulin (Ig) G, IgA, and neutralizing antibody responses at week 2 were all significantly higher than 2 weeks after the last RV144 vaccination. IgG titers against glycoprotein (gp) 70V1V2 92TH023 increased 14-fold compared with 2 weeks after the last RV144 vaccination (14069 vs 999; P < .001). Groups 1 and 2 did not differ significantly from each other, whereas group 3 was similar to placebo recipients. Responses in groups 1 and 2 declined by week 24 but were boosted by the second vaccination, albeit at lower magnitude than for week 2.



In RV144 vaccinees, AIDSVAX B/E with or without ALVAC-HIV 6-8 years after initial vaccination generated higher humoral responses than after RV144, but these responses were short-lived, and their magnitude did not increase with subsequent boost.



NCT01435135.
Department of Disease Control, Ministry of Public Health, Nonthaburi.
Supachai
S
Rerks-Ngarm
Vaccine Trial Centre, Faculty of Tropical Medicine, Mahidol University, Bankok
Punnee
P
Pitisuttithum
US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring.|Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda.
Jean-Louis
JL
Excler
Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.
Sorachai
S
Nitayaphan
Vaccine Trial Centre, Faculty of Tropical Medicine, Mahidol University, Bankok
Jaranit
J
Kaewkungwal
Department of Disease Control, Ministry of Public Health, Nonthaburi.
Nakorn
N
Premsri
Department of Disease Control, Ministry of Public Health, Nonthaburi.
Prayura
P
Kunasol
Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.
Nicos
N
Karasavvas
Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.|US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring.|Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda.
Alexandra
A
Schuetz
Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.
Viseth
V
Ngauy
Global Solutions for Infectious Diseases, South San Francisco, California.
Faruk
F
Sinangil
The Emmes Corporation, Rockville, Maryland.
Peter
P
Dawson
Vaccine and Infectious Disease Division and Statistical Center for HIV/AIDS Research and Prevention, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Allan C
AC
deCamp
Sanofi Pasteur, Swiftwater, Pennsylvania.
Sanjay
S
Phogat
Sanofi Pasteur, Swiftwater, Pennsylvania.
Sanjay
S
Garunathan
Sanofi Pasteur, Swiftwater, Pennsylvania.
James
J
Tartaglia
Sanofi Pasteur, Swiftwater, Pennsylvania.
Carlos
C
DiazGranados
US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring.
Silvia
S
Ratto-Kim
US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring.|Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda.
Poonam
P
Pegu
US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring.|Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda.
Michael
M
Eller
Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.
Chitraporn
C
Karnasuta
Duke Human Vaccine Institute, Durham, North Carolina.|Department of Surgery, Duke University, Durham, North Carolina.
David C
DC
Montefiori
Duke Human Vaccine Institute, Durham, North Carolina.
Sheetal
S
Sawant
Duke Human Vaccine Institute, Durham, North Carolina.
Nathan
N
Vandergrift
Duke Human Vaccine Institute, Durham, North Carolina.
Saintedym
S
Wills
Duke Human Vaccine Institute, Durham, North Carolina.
Georgia D
GD
Tomaras
US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring.|Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda.
Merlin L
ML
Robb
US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring.
Nelson L
NL
Michael
US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring.
Jerome H
JH
Kim
US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring.|Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda.|Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.
Sandhya
S
Vasan
Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.|US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring.
Robert J
RJ
O'Connell
D016915:AIDS Vaccines / Q000008:administration & dosage*; D000328:Adult; D057134:Antibodies, Neutralizing / Q000097:blood; D016207:Cytokines / Q000276:immunology; D004311:Double-Blind Method; D005260:Female; D015483:HIV Antibodies / Q000097:blood; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015658:HIV Infections / Q000517:prevention & control*; D015497:HIV-1; D064368:Healthy Volunteers; D006801:Humans; D056724:Immunity, Humoral; D007117:Immunization, Secondary; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D013785:Thailand
D016915:AIDS Vaccines; C112734:AIDSVAX; C574872:AIDSVAX B-E; D057134:Antibodies, Neutralizing; D016207:Cytokines; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D007070:Immunoglobulin A; D007074:Immunoglobulin G
HIV; RV144; prime-boost.; vaccine