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Sequential Immunization with gp140 Boosts Immune Responses Primed by Modified Vaccinia Ankara or DNA in HIV-Uninfected South African Participants.
- Source :
-
PloS one [PLoS One] 2016 Sep 01; Vol. 11 (9), pp. e0161753. Date of Electronic Publication: 2016 Sep 01 (Print Publication: 2016). - Publication Year :
- 2016
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Abstract
- Background: 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.<br />Methods: 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.<br />Results: 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.<br />Conclusions: 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.<br />Trial Registration: ClinicalTrials.gov NCT01418235.<br />Competing Interests: 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, http://www.PLOSone.org/static/editorial.action#competing).
- Subjects :
- Adolescent
Adult
Antibodies, Neutralizing immunology
CD4-Positive T-Lymphocytes immunology
CD8-Positive T-Lymphocytes immunology
Female
HIV Seropositivity immunology
HIV-1 physiology
Humans
Male
Pregnancy
Safety
South Africa
Time Factors
Young Adult
HIV-1 immunology
Immunization, Secondary adverse effects
Immunization, Secondary methods
Vaccines, DNA immunology
Vaccinia immunology
env Gene Products, Human Immunodeficiency Virus adverse effects
env Gene Products, Human Immunodeficiency Virus immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 11
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 27583368
- Full Text :
- https://doi.org/10.1371/journal.pone.0161753