title: SIVmac239 MVA vaccine with and without a DNA prime, similar prevention of infection by a repeated dose SIVsmE660 challenge despite different immune responses.
abstract: BACKGROUND
  Vaccine regimens using different agents for priming and boosting have become popular for enhancing T cell and Ab responses elicited by candidate HIV/AIDS vaccines. Here we use a simian model to evaluate immunogenicity and protective efficacy of a recombinant modified vaccinia Ankara (MVA) vaccine in the presence and absence of a recombinant DNA prime. The simian vaccines and regimens represent prototypes for candidate HIV vaccines currently undergoing clinical testing.
  
  
  METHODS
  Recombinant DNA and MVA immunogens expressed simian immunodeficiency virus (SIV)mac239 Gag, PR, RT, and Env sequences. Vaccine schedules tested inoculations of MVA at months 0, 2, and 6 (MMM regimen) or priming with DNA at months 0 and 2 and boosting with MVA at months 4 and 6 (DDMM regimen). Twelve weekly rectal challenges with the heterologous SIV smE660 were initiated at 6 months following the last immunization.
  
  
  RESULTS
  Both regimens elicited similar 61-64% reductions in the per challenge risk of SIVsmE660 transmission despite raising different patterns of immune responses. The DDMM regimen elicited higher magnitudes of CD4 T cells whereas the MMM regimen elicited higher titers and greater avidity Env-specific IgG and more frequent and higher titer SIV-specific IgA in rectal secretions. Both regimens elicited similar magnitudes of CD8 T cells. Magnitudes of T cell responses, specific activities of rectal IgA Ab, and the tested specificities for neutralization and antibody-dependent cellular cytotoxicity did not correlate with risk of infection. However, the avidity of Env-specific IgG had a strong correlation with the per challenge risk of acquisition, but only for the DDMM group.
  
  
  CONCLUSIONS
  We conclude that for the tested immunogens in rhesus macaques, the simpler MMM regimen is as protective as the more complex DDMM regimen.
authors.affiliation: Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, United States.
authors.forename: Lilin
authors.initials: L
authors.lastname: Lai
authors.forename: Sue-Fen
authors.initials: SF
authors.lastname: Kwa
authors.forename: Pamela A
authors.initials: PA
authors.lastname: Kozlowski
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.forename: Tracy L
authors.initials: TL
authors.lastname: Nolen
authors.forename: Michael G
authors.initials: MG
authors.lastname: Hudgens
authors.forename: Welkin E
authors.initials: WE
authors.lastname: Johnson
authors.forename: Guido
authors.initials: G
authors.lastname: Ferrari
authors.forename: Vanessa M
authors.initials: VM
authors.lastname: Hirsch
authors.forename: Barbara K
authors.initials: BK
authors.lastname: Felber
authors.forename: George N
authors.initials: GN
authors.lastname: Pavlakis
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Earl
authors.forename: Bernard
authors.initials: B
authors.lastname: Moss
authors.forename: Rama Rao
authors.initials: RR
authors.lastname: Amara
authors.forename: Harriet L
authors.initials: HL
authors.lastname: Robinson
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D000917:Antibody Formation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D007111:Immunity, Cellular; D007115:Immunization Schedule; D007070:Immunoglobulin A / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood; D008253:Macaca mulatta; D008297:Male; D009500:Neutralization Tests; D012007:Rectum / Q000276:immunology; D018449:SAIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control*; D015302:Simian Immunodeficiency Virus / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D007070:Immunoglobulin A; D007074:Immunoglobulin G; C560489:MVA vaccine; D018449:SAIDS Vaccines; D019444:Vaccines, DNA; D014765:Viral Vaccines