CROI 2024 Abstract eBook

Abstract eBook

Poster Abstracts

379

Sex-Based Differences in Antibody Responses Induced by a Native-Like HIV-1 Envelope Trimer Vaccine Emma Reiss, Karlijn van der Straten 1 , Marinus Liesdek 1 , Annelou L. van der Veen 2 , Marloes Grobben 1 , Hongmei Gao 3 , Kelli Greene 3 , David C. Montefiori 3 , Maarten Soeters 1 , Michelle J. Klouwens 1 , Jan M. Prins 1 , Marit van Gils 1 , Rogier W. Sanders 1 , Godelieve J. de Bree 1 1 University of Amsterdam, Amsterdam, Netherlands, 2 Amsterdam UMC, location University of Amsterdam, Amsterdam, the Netherlands, 3 Duke University School of Medicine, Durham, NC, USA Background: A protective vaccine would be the most powerful tool towards reducing HIV-1 infections worldwide and sustainably ending the AIDS epidemic as a public health threat. We assessed the safety and immunogenicity of ConM SOSIP.v7, a native-like envelope trimer vaccine based on an HIV-1 group M consensus sequence, in HIV-negative adults. Methods: 24 individuals were enrolled in a phase 1 clinical trial to receive three dosages of adjuvanted ConM SOSIP.v7 (baseline, eight and 24 weeks) and followed-up for one year thereafter. Out of 23 per-protocol vaccine recipients, 10 received a one-fifth fractional third dose, aimed to increase B cell somatic hypermutation. Outcomes included ConM-specific total immunoglobulin G (IgG), IgG subclasses, pseudovirus neutralisation and single B cell sequencing. Levels of sex hormones were measured over time. Results: The majority of adverse events were mild to moderate, self-limiting and similar between dosage groups and sexes. No serious adverse events were reported. Similar to non-human primates, adjuvanted ConM SOSIP.v7 was consistently capable of inducing an autologous neutralising antibody response in humans, which remained detectable in half of the participants six months after the final vaccination. Antibody binding to several heterologous envelope proteins could be detected in the majority of participants, but no neutralisation breath. No differences in serological outcomes could be attributed to the fractional third dose. Female born participants had an earlier increase in neutralising antibodies than males and had a 6.3-fold higher neutralisation titer post third vaccination. Sex-based differences in IgG1 and IgG4 subtype responses were also observed. Subtle correlations, both positive and negative, were seen between ConM-neutralisation, IgG2 and IgG3 levels on one hand, and oestradiol and testosterone on the other hand, but the small sample size limits drawing strong conclusions. Single B cell sequencing should reveal whether the fractional dose and/or sex influence B cell affinity maturation. Conclusion: The adjuvanted ConM SOSIP.v7 native-like trimer vaccine is safe and elicits a robust strain- specific neutralising response in nearly all recipients, making it an interesting boosting immunogen candidate. Females responded earlier and had a striking 6.3-fold higher neutralisation titer after the final vaccination. This study highlights that sex-based differences should be taken into consideration when assessing HIV-1 vaccine candidates and adjuvants.

Poster Abstracts

378

Adenosine Deaminase-1 Enhances HIV-Specific Responses to a HIV Trimeric Envelope DNA Vaccine Gina Cusimano 1 , David Joyner 1 , Emily Konopka 1 , Roshell Muir 1 , Gabriela Canziani 1 , Philip Barnette 2 , Iván del Moral-Sánchez 3 , Tom Bijl 3 , Jonne Snitselaar 3 , Kyra Woloszczuk 1 , Irwin M. Chaiken 1 , Ann J. Hessell 2 , Rogier W. Sanders 3 , Elias K. Haddad 1 , Michele A. Kutzler 1 1 Drexel College of Medicine, Philadelphia, PA, USA, 2 Oregon Health and Sciences University, Portland, OR, USA, 3 University of Amsterdam, Amsterdam, Netherlands Background: Human immunodeficiency virus (HIV) remains a prominent global health threat for which no prophylactic vaccine is available. Extensive research efforts have resulted in immunogens, including SOSIP trimers, that closely mimic the native envelope (Env) glycoprotein conformation and consistently induce autologous neutralizing responses. Recently, a novel triple tandem trimer (TTT) platform has been used to generate a plasmid encoding Env immunogen (pBG505-TTT) that expresses only as trimers, making it more suitable for nucleic acid vaccines. We have demonstrated that adenosine deaminase-1 (ADA-1) is critical to the T follicular helper (TFH) function and survival. In fact, ADA-1-induced TFH function that improved the magnitude and durability of both cellular and humoral vaccine immune responses in vivo. We therefore hypothesized that ADA-1 combined with the improved HIV envelope antigen pBG505-TTT would result in enhanced qualitative and quantitative humoral and cellular HIV specific responses. Methods: Mice were immunized intramuscularly with 1, 5, or 10μg of pBG505-TTTalone or were co- immunized with 10μg of plasmid encoded adenosine deaminase-1 (pADA). A separate group of mice were immunized with both DNA as described and 10ug of trimeric Env recombinant protein (rBG505-SOSIP) with adjuvants Alum or MF59. Mice were bled on day 21 post 2 immunizations (D21P2) and day 14 post 3 immunizations (D14P3) to evaluate humoral responses via ELISA, surface plasmon resonance, and neutralization assays. Cellular responses were evaluated on D14P3 via ELISpot assays, T cell intracellular cytokine staining and antigen specific memory B cell staining via flow cytometry. Results: Mice co-immunized with pADA and 1μg pBG505-TTT displayed significantly increased Env specific antibody titers as early as D21P2. pADA and 10μg pBG505-TTTco-immunized mice exhibited Env specific antibody with enhanced affinity and increased Env specific memory B cells when compared to non-adjuvanted counterparts. Mice immunized with 10μg pBG505-TTT, pADA, rBG505-SOSIPand alum exhibited enhanced neutralization compared to their non-pADA adjuvanted counterparts. Mice receiving pADA and 1μg or 5 μg pBG505-TTT exhibited enhanced Env specific T cell activation, cytokine polyfunctionality, and degranulation. Conclusion: These data demonstrate that pADA enhances both cellular and humoral immunity in a dose sparing manner against HIV Env making it a promising adjuvant for HIV targeting vaccines.

380

IgG and Fc Receptor Genetic Variation Associates With Functional Antibody Responses in HVTN 108 Song Young Oh 1 , Haleigh Conley 2 , Nigel Garrett 3 , One Dintwe 4 , Guido Ferrari 2 , Georgia D. Tomaras 2 , Dan Geraghty 4 , Cliburn Chan 2 , Justin Pollara 2 , for the HVTN 108 Study Team 1 Duke University, Durham, NC, USA, 2 Duke University School of Medicine, Durham, NC, USA, 3 University of KwaZulu-Natal, Durban, South Africa, 4 Fred Hutchinson Cancer Center, Seattle, WA, USA Background: The HVTN108 trial evaluated the immunogenicity of a DNA prime, adjuvanted protein boost vaccine regimen in the US and South Africa. We defined the IgG antibody Fc and Fc receptor (FcR) genotypes in the study population to test our hypothesis that IgG and FcR genetic variation can affect vaccine-elicited functional antibody responses. Methods: HVTN108 enrolled 334 participants in treatment (n=310) and placebo (n=24) groups. The genotypes of IgG Fc and FcRs were determined by targeted PCR amplification and Illumina next-generation sequencing. Vaccine-

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CROI 2024