title: Toll-like receptor 7/8 (TLR7/8) and TLR9 agonists cooperate to enhance HIV-1 envelope antibody responses in rhesus macaques.
abstract: The development of a vaccine that can induce high titers of functional antibodies against HIV-1 remains a high priority. We have developed an adjuvant based on an oil-in-water emulsion that incorporates Toll-like receptor (TLR) ligands to test whether triggering multiple pathogen-associated molecular pattern receptors could enhance immunogenicity. Compared to single TLR agonists or other pairwise combinations, TLR7/8 and TLR9 agonists combined were able to elicit the highest titers of binding, neutralizing, and antibody-dependent cellular cytotoxicity-mediating antibodies against the protein immunogen, transmitted/founder HIV-1 envelope gp140 (B.63521). We further found that the combination of TLR7/8 and TLR9 agonists was associated with the release of CXCL10 (IP-10), suggesting that this adjuvant formulation may have optimally stimulated innate and adaptive immunity to elicit high titers of antibodies.
  
  
  OBJECTIVE
  Combining TLR agonists in an adjuvant formulation resulted in higher antibody levels compared to an adjuvant without TLR agonists. Adjuvants that combine TLR agonists may be useful for enhancing antibody responses to HIV-1 vaccines.
authors.affiliation: Duke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: M Anthony
authors.initials: MA
authors.lastname: Moody
authors.forename: Sampa
authors.initials: S
authors.lastname: Santra
authors.forename: Nathan A
authors.initials: NA
authors.lastname: Vandergrift
authors.forename: Laura L
authors.initials: LL
authors.lastname: Sutherland
authors.forename: Thaddeus C
authors.initials: TC
authors.lastname: Gurley
authors.forename: Mark S
authors.initials: MS
authors.lastname: Drinker
authors.forename: Ashley A
authors.initials: AA
authors.lastname: Allen
authors.forename: Shi-Mao
authors.initials: SM
authors.lastname: Xia
authors.forename: R Ryan
authors.initials: RR
authors.lastname: Meyerhoff
authors.forename: Robert
authors.initials: R
authors.lastname: Parks
authors.forename: Krissey E
authors.initials: KE
authors.lastname: Lloyd
authors.forename: David
authors.initials: D
authors.lastname: Easterhoff
authors.forename: S Munir
authors.initials: SM
authors.lastname: Alam
authors.forename: Hua-Xin
authors.initials: HX
authors.lastname: Liao
authors.forename: Brandy M
authors.initials: BM
authors.lastname: Ward
authors.forename: Guido
authors.initials: G
authors.lastname: Ferrari
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.forename: Georgia D
authors.initials: GD
authors.lastname: Tomaras
authors.forename: Robert A
authors.initials: RA
authors.lastname: Seder
authors.forename: Norman L
authors.initials: NL
authors.lastname: Letvin
authors.forename: Barton F
authors.initials: BF
authors.lastname: Haynes
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D005260:Female; D015483:HIV Antibodies / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007114:Immunization; D008024:Ligands; D008253:Macaca mulatta; D008297:Male; D051199:Toll-Like Receptor 7 / Q000819:agonists* / Q000276:immunology; D051200:Toll-Like Receptor 8 / Q000819:agonists* / Q000276:immunology; D051217:Toll-Like Receptor 9 / Q000819:agonists* / Q000235:genetics / Q000276:immunology; D054299:env Gene Products, Human Immunodeficiency Virus / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D015483:HIV Antibodies; D008024:Ligands; D051199:Toll-Like Receptor 7; D051200:Toll-Like Receptor 8; D051217:Toll-Like Receptor 9; D054299:env Gene Products, Human Immunodeficiency Virus; C097729:gp140 envelope protein, Human immunodeficiency virus 1