title: Sequential Immunization with gp140 Boosts Immune Responses Primed by Modified Vaccinia Ankara or DNA in HIV-Uninfected South African Participants.
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.
  
  
  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.
  
  
  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.
  
  
  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.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01418235.
authors: 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.
authors: Gavin
authors: G
authors: Churchyard
authors: University of Kwa-Zulu Natal, Durban, South Africa.
authors: Koleka
authors: K
authors: Mlisana
authors: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States of America.
authors: Shelly
authors: S
authors: Karuna
authors: 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.
authors: Anna-Lise
authors: AL
authors: Williamson
authors: 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.
authors: Carolyn
authors: C
authors: Williamson
authors: National Institute for Communicable Diseases, National Health Laboratory Services, Sandringham, Johannesburg, South Africa.
authors: Lynn
authors: L
authors: Morris
authors: Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC, United States of America.
authors: Georgia D
authors: GD
authors: Tomaras
authors: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States of America.|Department of Laboratory Medicine, University of Washington, Seattle, WA, United States of America.
authors: Stephen C
authors: SC
authors: De Rosa
authors: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States of America.
authors: Peter B
authors: PB
authors: Gilbert
authors: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States of America.
authors: Niya
authors: N
authors: Gu
authors: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States of America.
authors: Chenchen
authors: C
authors: Yu
authors: National Institute for Communicable Diseases, National Health Laboratory Services, Sandringham, Johannesburg, South Africa.
authors: Nonhlanhla N
authors: NN
authors: Mkhize
authors: National Institute for Communicable Diseases, National Health Laboratory Services, Sandringham, Johannesburg, South Africa.
authors: Tandile
authors: T
authors: Hermanus
authors: Vaccine Research Program, Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States of America.
authors: Mary
authors: M
authors: Allen
authors: Vaccine Research Program, Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States of America.
authors: Michael
authors: M
authors: Pensiero
authors: Novartis Vaccines and Diagnostics, Cambridge, MA, United States of America.
authors: Susan W
authors: SW
authors: Barnett
authors: 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.
authors: Glenda
authors: G
authors: Gray
authors: Desmond Tutu HIV Centre, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
authors: Linda-Gail
authors: LG
authors: Bekker
authors: Laboratory for AIDS Vaccine Research and Development, Duke University Medical Center, Durham, NC, United States of America.
authors: David C
authors: DC
authors: Montefiori
authors: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States of America.
authors: James
authors: J
authors: Kublin
authors: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States of America.|Department of Laboratory Medicine, University of Washington, Seattle, WA, United States of America.
authors: Lawrence
authors: L
authors: Corey
mesh_terms: D000293:Adolescent; D000328:Adult; D057134:Antibodies, Neutralizing / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D006679:HIV Seropositivity / Q000276:immunology; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology; D006801:Humans; D007117:Immunization, Secondary / Q000009:adverse effects* / Q000379:methods*; D008297:Male; D011247:Pregnancy; D012449:Safety; D013019:South Africa; D013997:Time Factors; D019444:Vaccines, DNA / Q000276:immunology*; D014615:Vaccinia / Q000276:immunology*; D055815:Young Adult; D054299:env Gene Products, Human Immunodeficiency Virus / Q000009:adverse effects* / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D019444:Vaccines, DNA; D054299:env Gene Products, Human Immunodeficiency Virus; C097729:gp140 envelope protein, Human immunodeficiency virus 1