title: Cellular immunity elicited by human immunodeficiency virus type 1/ simian immunodeficiency virus DNA vaccination does not augment the sterile protection afforded by passive infusion of neutralizing antibodies.
abstract: High levels of infused anti-human immunodeficiency virus type 1 (HIV-1) neutralizing monoclonal antibodies (MAbs) can completely protect macaque monkeys against mucosal chimeric simian-human immunodeficiency virus (SHIV) infection. Antibody levels below the protective threshold do not prevent infection but can substantially reduce plasma viremia. To assess if HIV-1/SIV-specific cellular immunity could combine with antibodies to produce sterile protection, we studied the effect of a suboptimal infusion of anti-HIV-1 neutralizing antibodies in macaques with active cellular immunity induced by interleukin-2 (IL-2)-adjuvanted DNA immunization. Twenty female macaques were divided into four groups: (i). DNA immunization plus irrelevant antibody, (ii). DNA immunization plus infusion of neutralizing MAbs 2F5 and 2G12, (iii). sham DNA plus 2F5 and 2G12, and (iv). sham DNA plus irrelevant antibody. DNA-immunized monkeys developed CD4 and CD8 T-cell responses as measured by epitope-specific tetramer staining and by pooled peptide ELISPOT assays for gamma interferon-secreting cells. After vaginal challenge, DNA-immunized animals that received irrelevant antibody became SHIV infected but displayed lower plasma viremia than control animals. Complete protection against SHIV challenge occurred in three animals that received sham DNA plus MAbs 2F5 and 2G12 and in two animals that received the DNA vaccine plus MAbs 2F5 and 2G12. Thus, although DNA immunization produced robust HIV-specific T-cell responses, we were unable to demonstrate that these responses contributed to the sterile protection mediated by passive infusion of neutralizing antibodies. These data suggest that although effector T cells can limit viral replication, they are not able to assist humoral immunity to prevent the establishment of initial infection.
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. jmascola@nih.gov
authors.forename: John R
authors.initials: JR
authors.lastname: Mascola
authors.forename: Mark G
authors.initials: MG
authors.lastname: Lewis
authors.forename: Thomas C
authors.initials: TC
authors.lastname: VanCott
authors.forename: Gabriela
authors.initials: G
authors.lastname: Stiegler
authors.forename: Hermann
authors.initials: H
authors.lastname: Katinger
authors.forename: Michael
authors.initials: M
authors.lastname: Seaman
authors.forename: Kristin
authors.initials: K
authors.lastname: Beaudry
authors.forename: Dan H
authors.initials: DH
authors.lastname: Barouch
authors.forename: Birgit
authors.initials: B
authors.lastname: Korioth-Schmitz
authors.forename: Georgia
authors.initials: G
authors.lastname: Krivulka
authors.forename: Anna
authors.initials: A
authors.lastname: Sambor
authors.forename: Brent
authors.initials: B
authors.lastname: Welcher
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Douek
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.forename: John W
authors.initials: JW
authors.lastname: Shiver
authors.forename: Pascal
authors.initials: P
authors.lastname: Poignard
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Burton
authors.forename: Norman L
authors.initials: NL
authors.lastname: Letvin
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D018791:CD4 Lymphocyte Count; D005260:Female; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D007116:Immunization, Passive; D007376:Interleukin-2 / Q000494:pharmacology; D008253:Macaca mulatta; D009500:Neutralization Tests; D018449:SAIDS Vaccines / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000517:prevention & control*; D015302:Simian Immunodeficiency Virus / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology*; D014621:Vagina / Q000821:virology
chemical_list: D000914:Antibodies, Viral; D007376:Interleukin-2; D018449:SAIDS Vaccines; D019444:Vaccines, DNA