CROI 2020 Abstract eBook

Abstract eBook

Poster Abstracts

RhCMV was unable to elicit unconventionally restricted CD8+ T cells in MCM suggesting a species barrier for viral vector function. Methods: To determine if non-classical T cell priming and protection against mucosal SIV challenge is restricted to RhCMV-vaccination of RM or a universal phenomenon, we constructed a ’68-1 like’ cynomolgus CMV expressing SIV antigens (CyCMV/SIV). We vaccinated eight MCM with CyCMV/SIV and monitored multiple immune parameters in the animals including transgene-specific CD4+ and CD8+ T cell responses in blood and BAL. We challenged the eight vaccinated MCM and eight unvaccinated controls with repeated, limiting-dose, intrarectal SIVmac239 to assess vaccine-mediated protection. Results: CyCMV/SIV vaccinated MCM generated unconventionally, MHC-II- and MHC-E-restricted T cell responses comparable to RhCMV/SIV vaccinated rhesus macaques. Upon challenge with SIVmac239, 50% of CyCMV/SIV vaccinated MCM stringently controlled SIVmac239 replication, defined as no plasma viremia and the development of T cell responses against SIV proteins absent from the vaccine. Acquisition and subsequent control of SIV was confirmed by cell- associated viral loads and adoptive transfer to naïve MCM of tissue biopsies from CyCMV/SIV-protected animals. Conclusion: Thus, we have confirmed the distinct immunologic and protective phenotype induced by CMV vaccines in a second nonhuman primate species with immunogenetics reflective of humans, indicating that these results are not unusual species-specific traits of RM or RhCMV and that 68-1 like HCMV/ HIV vaccines might similarly recapitulate unconventional T cell restriction and protect against HIV. 297LB SUPERIOR PROTECTION AGAINST SHIV INFECTION BY SAME SITE DNA- PROTEIN COIMMUNIZATION Barbara K. Felber 1 , Zhongyan Lu 1 , Xintao Hu 1 , Antonio Valentin 1 , Margherita Rosati 1 , Joshua A. Weiner 2 , Xiaoying Shen 3 , Georgia Tomaras 3 , Celia C. Lebranche 3 , David Venzon 4 , George Shaw 5 , Guido Ferrari 3 , Margaret Ackerman 2 , Barton F. Haynes 3 , George N. Pavlakis 1 1 National Cancer Institute, Frederick, MD, USA, 2 Dartmouth College, Hanover, NH, USA, 3 Duke University, Durham, NC, USA, 4 National Cancer Institute, Bethesda, MD, USA, 5 University of Pennsylvania, Philadelphia, PA, USA Background: We compared immunogenicity and protective efficacy of an HIV vaccine comprised of DNA (env and gag) and Env proteins by co-administration of DNA and Protein in the same muscle or by separate administration of the DNA and Protein components in contralateral sites. Methods: Female rhesus macaques (20 animals/group) were immunized with a 6-valent vaccine including DNA plasmids expressing membrane-anchored gp145 Env sequentially isolated from a HIV-1 infected individual (CH505). The DNA was delivered by IM injection followed by in vivo electroporation. The vaccine also included a gp120 Env protein component matching the sequences encoded by the plasmid DNA and adjuvanted in GLA-SE. The DNA and protein vaccine components were administered in the same anatomical sites (‘Co- administration’) or in contralateral sites (‘Separate Administration’) After 6 vaccinations in 4-month intervals, the macaques were challenged by weekly intravaginal exposures with low dose T/F tier-2 SHIV CH505 stock. Results: Only macaques in the co-administration vaccine group were protected against SHIV CH505 acquisition, with a 67% risk reduction per exposure after 15 weekly IVAG challenges. Macaques in the co-administration group developed higher Env-specific humoral and cellular immune responses. Non-neutralizing Env antibodies, ADCC and antibodies binding to Fc-gamma Receptor IIIa were associated with decreased transmission risk. These data suggest that simultaneous recognition, processing and presentation of DNA + Env protein in the same draining lymph node play a critical role in the development of protective immunity. Conclusion: Co-immunization of DNA+Protein in the same muscle is superior for inducing protective immune responses against repeated tier-2 SHIV challenge. The advantage of co-immunization vaccine regimens targeting immunogens to the same draining LN could also be beneficial to other vaccine modalities and other pathogens. 298 DOLUTEGRAVIR INCREASES B CELLS AND RESTING MEMORY B CELLS IN RV254 Supranee Buranapraditkun 1 , Eugène Kroon 2 , Hiroshi Takata 3 , Suthat Chottanapund 2 , Carlo Sacdalan 2 , Duanghathai Suttichom 2 , Ratchapong Kanaprach 2 , Somporn Tipsuk 2 , Khunthalee Benjapornpong 2 , Bessara Nuntapinit 4 , Merlin L. Robb 5 , Jintanat Ananworanich 5 , Sandhya Vasan 5 , Lydie

Trautmann 3 , for the on behalf of the SEARCH010/RV254/SEARCH013/RV304 Study group 1 Chulalongkorn University, Bangkok, Thailand, 2 SEARCH, Bangkok, Thailand, 3 Henry M Jackson Foundation, Silver Spring, MD, USA, 4 Armed Forces Research Institute of Medical Sciences in Bangkok, Bangkok, Thailand, 5 Henry M Jackson Foundation, Bethesda, MD, USA Background: Early initiation of antiretroviral therapy (ART) in acute HIV infection (AHI) could help preempt evasion and damage of the immune system by HIV. Use of the integrase inhibitor Dolutegravir (DTG) and 2NRTIs is the new standard regimen. However, the influence of these drugs on the recovery of immune cells in blood and lymph node (LN) tissue has not been well studied. To address this, we assessed differences in B cell populations in Thai participants randomized to switch from 2NRTI+EFV to 2NRTI+DTG. Methods: Cryopreserved peripheral blood mononuclear cells (PBMCs) and lymph node mononuclear cells (LNMCs) from 27 AHI treated Thai participants enrolled in the RV254 cohort were analyzed. Participants were grouped based on ART regimen: those randomized to switch from 2NRTI+EFV to 2NRTI+DTG (n=13; 6-22 mos EFV followed by 9-20 mos DTG) and those who remained on 3TC/TDF/EFV (n=14; range 6-22 mos). Eighteen uninfected individuals (HIV–) enrolled in RV304 were included for comparison. B cells were characterized by flow cytometry. Results: The frequencies of CD19+ B cells were significantly decreased in PBMCs but not LNMCs of 2NRTI+EFV treated compared to HIV– participants (p<0.05), but were recovered in those who switched to DTG. The frequencies of resting memory B cells (RM; CD21+CD27+IgG+CD20+) were significantly decreased in both PBMCs and LNMCs of the 2NRTI+EFV group (Fig 1a), whereas the frequencies of tissue-like memory B cells (TLM) were significantly increased compared to HIV– participants (p<0.05; Fig 1b). 2NRTI+DTG treated participants had recovered frequencies of RM B cells, but lower frequencies of TLM and activated memory B cells (AM) compared to HIV– participants and non-switched EFV-treated participants (p<0.05; Fig 1c). Conclusion: Our data show that switching from 2NRTI+EFV to 2NRTI+DTG could aid in recovery of B cell populations in the blood and LN, although the number of LNMC samples in the 2NRTI+DTG group in the present study limits definitive conclusions for this compartment. We observed higher frequencies of B cells and RM B cells in both PBMCs and LNMCs after switching from 2NRTI+EFV to 2NRTI+DTG. Further, 2NRTI+DTG treated participants had fewer AM and TLM B cells, the latter of which have an exhausted phenotype. These data suggest that switching from EFV to DTG may be beneficial to limit activation and exhaustion in the B cell compartment of participants who initiated treatment in AHI.

Poster Abstracts

299 CHARACTERIZING ANTIBODY RESPONSES IN ART-TREATED INDIVIDUALS Andrew B. Wilson 1 , Yanqin Ren 2 , Eva M. Stevenson 2 , R. Brad Jones 2 , Rebecca Lynch 1 1 George Washington University, Washington, DC, USA, 2 Weill Cornell Medicine, New York, NY, USA Background: Although suppression of HIV has become possible through antiretroviral therapy (ART), ART-treated individuals must maintain therapy to avoid rebound from a viral reservoir. Strategies to limit or clear this reservoir are urgently needed. Research has shown that individuals infected for longer prior to receiving ART harbor greater reservoir diversity, but may also have higher anti-HIV antibody titers. The roles that infection length and viral diversity play in the humoral response must be further studied to inform approaches to clearing infection. Here, we aim to clarify a role, if any, for autologous antibodies in these treatments by characterizing their function in individuals on different lengths of ART. Methods: Plasma was collected from 8 HIV+males on ART. Bulk IgG was isolated and normalized concentrations were tested for binding to gp41 and

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