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PLoS One. 2016 Sep 1;11(9):e0161753. doi: 10.1371/journal.pone.0161753. eCollection 2016.

Sequential Immunization with gp140 Boosts Immune Responses Primed by Modified Vaccinia Ankara or DNA in HIV-Uninfected South African Participants.

Author information

Aurum Institute for Health Research, Klerksdorp, South Africa.
School of Public Health, University of Witwatersrand, Johannesburg, South Africa.
Advancing Care and Treatment for TB and HIV, Medical Research Council Collaborating Centre, Klerksdorp, South Africa.
University of Kwa-Zulu Natal, Durban, South Africa.
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States of America.
Institute of Infectious Disease and Molecular Medicine, Division of Medical Virology, University of Cape Town, Cape Town, South Africa; National Health Laboratory Services, Observatory, Cape Town, South Africa.
National Institute for Communicable Diseases, National Health Laboratory Services, Sandringham, Johannesburg, South Africa.
Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC, United States of America.
Department of Laboratory Medicine, University of Washington, Seattle, WA, United States of America.
Vaccine Research Program, Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States of America.
Novartis Vaccines and Diagnostics, Cambridge, MA, United States of America.
South African Medical Research Council, Cape Town, South Africa.
Perinatal HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Braamfontein, Johannesburg, South Africa.
Desmond Tutu HIV Centre, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
Laboratory for AIDS Vaccine Research and Development, Duke University Medical Center, Durham, NC, United States of America.



The safety and immunogenicity of SAAVI DNA-C2 (4 mg IM), SAAVI MVA-C (2.9 x 109 pfu IM) and Novartis V2-deleted subtype C gp140 (100 mcg) with MF59 adjuvant in various vaccination regimens was evaluated in HIV-uninfected adults in South Africa.


Participants at three South African sites were randomized (1:1:1:1) to one of four vaccine regimens: MVA prime, sequential gp140 protein boost (M/M/P/P); concurrent MVA/gp140 (MP/MP); DNA prime, sequential MVA boost (D/D/M/M); DNA prime, concurrent MVA/gp140 boost (D/D/MP/MP) or placebo. Peak HIV specific humoral and cellular responses were measured.


184 participants were enrolled: 52% were female, all were Black/African, median age was 23 years (range, 18-42 years) and 79% completed all vaccinations. 159 participants reported at least one adverse event, 92.5% were mild or moderate. Five, unrelated, serious adverse events were reported. The M/M/P/P and D/D/MP/MP regimens induced the strongest peak neutralizing and binding antibody responses and the greatest CD4+ T-cell responses to Env. All peak neutralizing and binding antibody responses decayed with time. The MVA, but not DNA, prime contributed to the humoral and cellular immune responses. The D/D/M/M regimen was poorly immunogenic overall but did induce modest CD4+ T-cell responses to Gag and Pol. CD8+ T-cell responses to any antigen were low for all regimens.


The SAAVI DNA-C2, SAAVI MVA-C and Novartis gp140 with MF59 adjuvant in various combinations were safe and induced neutralizing and binding antibodies and cellular immune responses. Sequential immunization with gp140 boosted immune responses primed by MVA or DNA. The best overall immune responses were seen with the M/M/P/P regimen.


[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

The authors have read the journal's policy and the authors of this manuscript have the following competing interests: MA and MP are employed by the National Institute of Allergy and Infectious Diseases (NIAID), the study sponsor. GC, KM, SK, CW, A-LW, LM, GDT, SCD, PG, NG, CY, GG, LGB, DCM, JK, LC were recipients of NIAID funding, and this publication is a result of activities funded by NIAID. MA and MP were not involved with the process of funding these awards, nor in their administration or scientific aspects, and, in accordance with NIAID policies, are deferred from decisions regarding funding of coauthors for a requisite period. This study was also partly funded by Novartis Vaccines. At the time the study was conducted, Susan W. Barnett was an employee and stakeholder of Novartis Vaccines and Diagnostics. This does not alter our adherence to PLOS ONE policies on sharing data and materials (as detailed online in the guide for authors,

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