CROI 2019 Abstract eBook
follow up period was associated with higher survival (HR: 0.141, 95% CI 0.058- 0.348, p<0001). Conclusion: Although therapies for both BL and HIV have improved over time, BL incidence among HIV positive veterans did not improve between 2000 and 2016. Survival after BL diagnosis in HIV positive male veterans remains dismal as compared to their HIV negative counterparts, although veterans with prolonged periods of undetectable viral load showed better survival. Further research is needed to improve treatment and outcomes for this aggressive lymphoma in PLWH.
Optimization of functional antibody responses hypothesized to correlate with protection in mucosal compartments may increase vaccine efficacy. 294 A VACCINE TARGETING HIV MATURATION PROTECTS AGAINST VAGINAL SIVMAC251 ACQUISITION Hongzhao Li 1 , Qingsheng Li 2 , Eva Rakasz 3 , Nancy Schultz-Darken 3 , Maria J. Alonso 4 , James Whitney 5 , Francis Plummer 1 , Ma Luo 1 , for the Dr. Ma Luo’s group 1 University of Manitoba, Winnipeg, MB, Canada, 2 University of Nebraska–Lincoln, Lincoln, NE, USA, 3 University of Wisconsin–Madison, Madison, WI, USA, 4 University of Santiago de Compostela, Santiago de Compostela, Spain, 5 Harvard University, Boston, MA, USA Background: After over three decades of research, an effective vaccine against HIV-1 remains elusive. Great genetic diversity, rapid mutation and targeting CD4+ T cells are major challenges for developing an effective HIV vaccine. Studies have shown that inflammation activates CD4+ T cells and enhances susceptibility to HIV-1. Current candidate HIV vaccines focus on generating strong, broad and durable immune responses to deal with genetic diversity and rapid mutation of HIV-1. None of them have addressed the challenges to develop a vaccine for a virus targeting the immune system itself. Learning from Natural immunity observed from a group of HIV resistant Kenyan sex workers we developed a novel HIV vaccine approach, targeting the sequences surrounding the 12 protease cleavage sites (PCS vaccine). In this study we evaluated the efficacy of protection of this novel vaccine using a Macaque/SIV model. Methods: Thirty-Two female Mauritian Cynomolgus macaques were immunized with VSV vector, PCS vaccine (rVSVpcs and NANOpcs), Gag/Env vaccine (rVSVgag/env and NANPgag/env), or NANOpcs vaccine (3 PCS peptides). Mucosal and systemic antibodies, as well as CVL inflammatory cytokines were analyzed with an in-house developed multiplexed Bead array assay using BioPLex200, and Western blot. T cell responses were analyzed using INF-gamma ELISPOT assay and FACS analysis. After immunization and boosts the vaccinated macaques and controls were challenged intravaginally with SIVmac251 (250 TCID50) every two weeks until majority of controls were infected. Keplan-Meier survival analysis and Cox regression model were used to compare vaccine efficacy. Results: Both PCS vaccine and Gag/Env vaccine significantly protected macaques from pathogenic SIVmac251 infection (p=0.04) after 6 intravaginal challenges. Per-exposure risk reduction was >80%. The magnitude of mucosal neutralizing antibody level and the magnitude of antigen specific INF-gamma ELISPOT response after the last boost do not correlate with protection. The higher magnitude of mucosal MIP-1β/CCL4 (after the last boost) is correlated with an increased risk of SIVmac251 infection. Conclusion: Our study showed for the first time that a candidate HIV vaccine targeting sequences surrounding the 12 protease cleavage sites, other than full Gag and Env can provide significant protection against pathogenic SIVmac251 intravaginal challenges. Generating immune response while modulating mucosal inflammatory environment may be the key for an effective prophylactic HIV vaccine.
293 LONG BOOST INTERVALS OF ALVAC-HIV/AIDSVAX B/E INCREASED GENITAL HIV ENV IGG RESPONSES
Siriwat Akapirat 1 , Supachai Rerks-Ngarm 2 , Punnee Pitisutthithum 3 , Sorachai Nitayaphan 1 , Suwat Chariyalertsak 4 , Sanjay Phogat 5 , Faruk Sinangil 6 , Jean-Louis Excler 7 , Merlin L. Robb 8 , Nelson L. Michael 8 , Jerome H. Kim 7 , Nicos Karasavvas 9 , Sandhya Vasan 8 , Robert J. O’Connell 1 , for the RV305 and RV306 Study Groups 1 Armed Forces Research Institute of Medical Sciences in Bangkok, Bangkok, Thailand, 2 Ministry of Public Health, Nonthaburi, Thailand, 3 Mahidol University, Bangkok, Thailand, 4 Research Institute for Health Sciences, Chiang Mai University, Chiang Mai, Thailand, 5 Sanofi Pasteur, Swiftwater, PA, USA, 6 Global Solutions for Infectious Diseases, San Francisco, CA, USA, 7 International Vaccine Institute, Seoul, South Korea, 8 US Military HIV Research Program, Silver Spring, MD, USA, 9 Walter Reed Army Institute of Research, Silver Spring, MD, USA Background: Anogenital mucosae are the primary sites of HIV acquisition. Boost with AIDSVAX B/E, with or without ALVAC-HIV, after receiving the RV144 vaccine regimen in the RV305 and RV306 trials induced HIV Env-specific IgG in cervico-vaginal mucus (CVM) and seminal plasma (SP). Here, we evaluated the effect of boosting intervals to magnitude and persistence of antibody responses in CVM and SP. Methods: IgG and IgA to gp120 and gp70V1V2 scaffold proteins two weeks post vaccination in CVM and SP were quantified by ELISA. The effect of boosting interval was assessed by comparing peak responses after receiving the RV144 vaccine series with peak responses following a late vaccine boost of AIDSVAX B/E, with or without ALVAC-HIV, at varying boosting intervals. Results: IgG to gp120 A244gD- and gp70V1V2 scaffold proteins in CVM significantly increased with late ALVAC-HIV/AIDSVAX B/E boost at 15 months and 18 months compared to peak responses post received RV144 series (A244gD-/ gp70V1V2 titer range=800-1600/38-300), p<0.03. IgG to gp70V1V2 CaseA2 in CVM increased after the additional boost of AIDSVAX B/E in participants who received boost of ALVAC-HIV/AIDSVAX B/E or AIDSVAX B/E alone 3-4 years earlier (titer=50), p<0.05. In SP, boosting with ALVAC-HIV/AIDSVAX B/E at 18 months led to significantly higher IgG to gp120 A244gD- (titer=100) and gp70V1V2 92TH023 (titer=25) compared to peak responses post RV144 series, p<0.05. Boosting with AIDSVAX B/E at 9-12 years significantly increased IgG to gp120 MNgD- in SP (titer=150) compared to peak responses post received RV144 series (titer=50), p=0.02. Fold decrease of IgG to all proteins tested over 24 weeks post final vaccination in CVMwas not significantly different among boosting groups. In SP, fold decrease of IgG to 92TH023 over 24 weeks post late AIDSVAX B/E boost in participants who received boost of ALVAC-HIV/AIDSVAX B/E or AIDSVAX B/E alone 3-4 years earlier was significantly lower than those who received late boost of ALVAC-HIV/AIDSVAX B/E at 18 months (p<0.03). HIV Env- specific IgA was not detected in any samples tested by ELISA. Conclusion: Late boosts with AIDSVAX B/E, with or without ALVAC-HIV, produced higher peak HIV Env-specific IgG in CVM and SP at longer boosting intervals. Additional boosting with AIDSVAX B/E improved persistence of IgG to gp70V1V2 92TH023 in SP (measured by fold decrease over 24 weeks).
295 SIV- AND HIV-SPECIFIC IMMUNE RESPONSES ELICITED BY PIV5 PRIME/ VLP BOOST VACCINATION Biao He 1 , Peng Xiao 2 , Krista Dienger-Stambaugh 3 , Michelle Robillard 4 , Karnail Singh 3 , Francois Villinger 2 , Paul Spearman 3 1 University of Georgia, Athens, GA, USA, 2 University of Louisiana at Lafayette, Lafayette, LA, USA, 3 Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA, 4 University of Cincinnati, Cincinnati, OH, USA Background: An ideal preventive HIV vaccine may be expected to generate immune protection at mucosal ports of entry and systemically. Parainfluenza virus type 5 (PIV5) is a paramyxovirus that is non-pathogenic in humans and
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