Co-immunization of DNA and Protein in the Same Anatomical Sites Induces Superior Protective Immune Responses against SHIV Challenge.

Journal Article (Journal Article)

We compare immunogenicity and protective efficacy of an HIV vaccine comprised of env and gag DNA and Env (Envelope) proteins by co-administration of the vaccine components in the same muscles or by separate administration of DNA + protein in contralateral sites in female rhesus macaques. The 6-valent vaccine includes gp145 Env DNAs, representing six sequentially isolated Envs from the HIV-infected individual CH505, and matching GLA-SE-adjuvanted gp120 Env proteins. Interestingly, only macaques in the co-administration vaccine group are protected against SHIV CH505 acquisition after repeated low-dose intravaginal challenge and show 67% risk reduction per exposure. Macaques in the co-administration group develop higher Env-specific humoral and cellular immune responses. Non-neutralizing Env antibodies, ADCC, and antibodies binding to FcγRIIIa are associated with decreased transmission risk. These data suggest that simultaneous recognition, processing, and presentation of DNA + Env protein in the same draining lymph nodes play a critical role in the development of protective immunity.

Full Text

Duke Authors

Cited Authors

  • Felber, BK; Lu, Z; Hu, X; Valentin, A; Rosati, M; Remmel, CAL; Weiner, JA; Carpenter, MC; Faircloth, K; Stanfield-Oakley, S; Williams, WB; Shen, X; Tomaras, GD; LaBranche, CC; Montefiori, D; Trinh, HV; Rao, M; Alam, MS; Vandergrift, NA; Saunders, KO; Wang, Y; Rountree, W; Das, J; Alter, G; Reed, SG; Aye, PP; Schiro, F; Pahar, B; Dufour, JP; Veazey, RS; Marx, PA; Venzon, DJ; Shaw, GM; Ferrari, G; Ackerman, ME; Haynes, BF; Pavlakis, GN

Published Date

  • May 12, 2020

Published In

Volume / Issue

  • 31 / 6

Start / End Page

  • 107624 -

PubMed ID

  • 32402293

Pubmed Central ID

  • PMC7329227

Electronic International Standard Serial Number (EISSN)

  • 2211-1247

Digital Object Identifier (DOI)

  • 10.1016/j.celrep.2020.107624

Language

  • eng

Conference Location

  • United States