CROI 2020 Abstract eBook

Abstract eBook

Poster Abstracts

allowed the identification of the lymph nodes of interest that had drained the HIVgp140 protein. A significantly higher number of vaccine-targeted APC migrated in draining LN of NHPs immunized by anti-CD40.Env-gp140 (mean of 184 cells/mm²) compared to control animals (mean of 69 cells/mm²). Moreover, the magnitude of HIV-Env specific IFN-γ T cell response was correlated to the number of vaccine-targeted cells observed in vivo within the LN. HIV-Env specific T cell responses in anti-CD40 vaccinated animals was superior to the control group at the peak of response, 2 weeks post boost (1028 and 450 SFC/10 6 PBMC, respectively; mean of 6 animals). Specific antibody titers against Clade C Env proteins were also greater in anti-CD40 group (1700 and 202 EC 50 , respectively) than in controls (840.8 and 77.5 EC 50 , respectively) at 5 weeks post boost. Magnitude of the cellular response after a second boost was correlated to the durability of the response measured 30 weeks after immunization. Conclusion: Altogether these results exhibited that CD40 targeting influences the early immune events within the draining LN then leading to stronger T and B cells responses. We also demonstrate that CD40 targeting in presence of adjuvant significantly improves vaccine immunogenicity without requiring priming with different type of vector or targeting strategy. The safety and efficacy of the CD40-targeted vaccine justify further development for future human clinical trials. 294 HARNESSING ORIGINAL ANTIGENIC SIN FOR PREVENTING MTCT OF HIV Ashley N. Nelson 1 , Maria Dennis 2 , Jesse F. Mangold 2 , Katherine N. Li 2 , Riley J. Mangan 1 , George Shaw 3 , Katharine J. Bar 3 , Barton F. Haynes 2 , M. Anthony Moody 2 , Justin Pollara 2 , Koen Van Rompay 4 , Kristina De Paris 5 , Sallie Permar 2 1 Duke University School of Medicine, Durham, NC, USA, 2 Duke Human Vaccine Institute, Durham, NC, USA, 3 University of Pennsylvania, Philadelphia, PA, USA, 4 University of California Davis, Davis, CA, USA, 5 University of North Carolina at Chapel Hill, Chapel Hill, NC, USA Background: Progress towards the elimination of pediatric HIV infection via mother to child transmission (MTCT) is limited by several factors, including inconsistent access and maternal adherence to ART. The development of a maternal vaccine that can synergize with current ART prophylaxis could overcome implementation challenges impeding achievement of an HIV-free generation. Both the epitope specificity of HIV envelope (Env)-specific antibody responses and autologous virus neutralization have been implicated in MTCT risk of HIV. Our goal was to evaluate the immunogenicity of a heterologous vaccine regimen to boost autologous HIV Env-specific antibody responses in SHIV.C.CH505.375H.dCT, and began a daily ART (TDF, FTC, dolutegravir) regimen at 12 weeks post-infection (wpi). Two weeks after ART initiation, RMs received 3 intramuscular doses of HIV b.63521/1086.c gp120 (n=6; vaccine group) or RSV (n=6; placebo group) vaccine with a TLR agonist adjuvant (StR8C) monthly. ART was discontinued after 12 weeks and RMs were monitored for viral rebound. Binding and functional antibody responses were also measured. Results: HIV Env vaccination in the setting of ART did not delay viral rebound. HIV Env gp120 vaccinated RMs exhibited peak antibody binding responses at 20 wpi (2 weeks post 2nd immunization), with enhanced IgG responses against b.63521 and 1086.c vaccine immunogens; as well as the challenge virus Env, SHIV.C.CH505. Plasma autologous virus (CH505.TF) neutralization was similar between the two groups upon treatment interruption, while ADCC responses were markedly boosted in Env vaccinated animals. Vaccinated RMs exhibited greater breadth in IgG antibody responses against various Env epitopes, with V3- and V1V2- specific responses against both the vaccine and challenge virus antigens. Conclusion: In conclusion, vaccination of SHIV-infected RMs in the setting of ART can boost IgG responses against the original infecting antigen, SHIV.C.CH505, and Env-specific antibody responses previously associated with low risk of MTCT. Our results suggest that a vaccine regimen administered to HIV-infected pregnant women could boost previously identified humoral correlates of reduced MTCT risk in humans. 295 TBK-1-DC VACCINE INDUCES POLYFUNCTIONAL T CELLS AND CONTROL OF HIV-1 IN THE BLT MOUSE Marta Calvet-Mirabent 1 , Maud Deruaz 2 , Serah Tanno 2 , Cristina Delgado- Arévalo 1 , Ildefonso Sánchez-Cerrillo 1 , Carla Serra Peinado 3 , María J. Buzón 3 , Ignacio Santos 4 , Jesús Sanz 4 , Lucio Jesus Garcia-Fraile Fraile 4 , M Ángeles Muñoz- Fernández 5 , Alejandro Balazs 2 , Vladimir Vrbanac 2 , Enrique Martin-Gayo 1 SHIV-infected, ART-suppressed, female rhesus macaques (RMs). Methods: Twelve female RMs were infected intravenously with

1 Universidad Autónoma de Madrid, Madrid, Spain, 2 Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA, 3 Hospital Universitario de la Vall d’Hebron, Barcelona, Spain, 4 Hospital Universitario de La Princesa, Madrid, Spain, 5 Hospital General Universitario Gregorio Marañón, Madrid, Spain Background: Dendritic cells (DC) are critical to induce protective antiviral T cell responses, but previous HIV-1 vaccine studies suggest that improvement of DC function is essential for boosting HIV-1 specific immunity. TANK-binding Kinase 1 (TBK-1) is a key regulator of DC maturation in response to HIV-1 and to prime polyfunctional specific T cells. Our objective is to evaluate the efficacy of a vaccine based on TBK1-engineered DCs controlling HIV-1 infection in vivo using the humanized bone marrow, liver and thymus (hBLT) mouse model. Methods: A total of 24 humanized hBLT-mice were generated for the study. A fraction of autologous CD34+ hematopoietic stem cells (HSC) were used to differentiate DC in the presence of FLT3L, IL-7, SCF and GMCSF. Three separate groups of 8 humanized hBLT-mice were injected with HSC-derived DCs cultured in media (MED), gag peptides alone (GAG) or in combination with 2´-3´-c-AMP and Poly-I:C TBK-1 adjuvants (GAG-ADJ) and infected intravenously with 10,000 TCID50 of JRCSF HIV-1. Plasma HIV-1 viral loads, polyfunctional T cell responses from peripheral blood and lymphoid tissue and CD4+ T cell counts were assessed at 3 and 6 weeks post-infection. Presence of CD8+ T cells and p24+ infected cells was determined by immunofluorescence in lymphoid nodes. Statistical differences were calculated using a Mann Whitney or a Chi-square tests. Results: All groups of hBLT-mice became infected with HIV-1, however animals vaccinated with autologous GAG-ADJ DCs exhibited a partial but significant reduction of HIV-1 plasma viral loads at 3 weeks p.i. compared to control groups (p=0.021). These differences were accompanied by higher polyfunctional profiles in circulating CD8+ T cells in the GAG-ADJ group (p=0.005), suggesting partial control of viral replication at early time points. At 6 weeks post-vaccination, plasma viral loads were similar across different groups of vaccinated mice, however Polyfunctional T cells were specifically observed in the spleen from GAG-ADJ and a less severe depletion of CD4+ T cell lymphocytes was detected in these animals compared to GAG mice (p=0.05 vs p=0.0078). Moreover, increased clusters of CD8+ T cells excluding infected HIV-1 p24+ cells from specific areas within the lymph node were also observed in these animals (p=0.001). Conclusion: Engineered TBK-1 DCs are able to improve parameters of immune control of HIV-1 infection in the hBLT-mouse model and might be useful for subsequent vaccine studies.

Poster Abstracts

296 CMV VACCINE VECTOR-INDUCED PROTECTION AGAINST SIV IN MAURITIAN CYNOMOLGUS MACAQUES

Justin Greene 1 , Daniel Malouli 1 , Nicholas Maier 1 , Abigail Ventura 1 , Roxanne Gilbride 1 , Whitney Weber 1 , Helen Wu 1 , Junwei Gao 1 , Michael K. Axthelm 1 , Jeremy Smedley 1 , Jeffrey D. Lifson 2 , Klaus Fruh 1 , Louis J. Picker 1 , Scott Hansen 1 , Jonah Sacha 1 1 Oregon Health and Sciences University, Portland, OR, USA, 2 Frederick National Laboratory for Cancer Research, Frederick, MD, USA Background: Strain 68-1 rhesus cytomegalovirus (CMV) vaccine vectors expressing simian immunodeficiency virus (SIV) antigens (RhCMV/SIV) prime broadly-targeted, unconventionally MHC-II- and MHC-E-restricted CD8+ T cell responses that stringently control SIV replication in vaccinated rhesus macaques (RM). However, RM express many more MHC-II and MHC-E alleles than humans, and it remains unclear if the unprecedented cellular immunity and control of SIV observed in RhCMV/SIV-vaccinated RM is due to the unique immunogenetics of RM or species-specific functions of RhCMV itself. In contrast to RMs, Mauritian cynomolgus macaques (MCM) exhibit reduced genetic diversity with immunogenetics that more closely resemble those of humans. However, 68-1

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