Title

Advances in combatting HIV with broadly neutralizing antibodies

Code

SY34

Session Type

Symposium

Track

Track A: Basic and translational science

Format

Hybrid

CME accreditation

Yes

ROOM/CHANNEL

Room 510/Channel 8

Date Time

01 August 14:15 - 15:15

Moderators

Amy CHUNG, University of Melbourne, Australia
Glenda GRAY, South African Medical Research Council, South Africa

Presentations in this session will focus on utilizing broadly neutralizing antibodies (bNAbs) to combat HIV. Vaccines that can elicit bNAb responses are leading candidates for prophylactic vaccines and would be a powerful tool in the response to HIV. Recent developments of mRNA vaccines formulated in lipid nanoparticles have proved to be a potent mode of immunization against infectious diseases, and gp160 mRNA can potentially elicit bNAb responses. Another promising approach relies on subsequent immunizations with SOSIP-stabilized trimers, which result in antibody affinity maturation, possibly leading to bNAb responses. Besides vaccination, genes encoding for bNAbs can be utilized in a gene therapy strategy by ex vivo generating bNAb-expressing B cells. This approach can be specific and directed so that different bNAbs are expressed. Finally, passive immunization with bNAbs has the potential to limit the acquisition of HIV. Importantly, four- to six-monthly injectable PrEP of bNAbs offers strong adherence advantages over daily PrEP or monthly injectables, especially in resource-limited settings and/or for marginalized people.

14:15 2 min	Introduction Amy CHUNG, University of Melbourne, Australia Glenda GRAY, South African Medical Research Council, South Africa

14:17 12 min	mRNA vaccine Barton HAYNES, Duke Human Vaccine Institute and the Center for HIV-AIDS Vaccine Immunology, United States

14:29 12 min	First-in-human Phase 1 trials with SOSIP Env trimers Godelieve DE BREE, Amsterdam University Medical Center, Netherlands	Slides PDF Image

14:41 12 min	Overcoming 'improbable mutations' Kevin SAUNDERS, Duke University Medical Center, United States

14:53 12 min	bNAB infusion Lynn MORRIS, National Institute for Communicable Diseases, South Africa	Slides

15:05 10 min	Q&A Amy CHUNG, University of Melbourne, Australia Godelieve DE BREE, Amsterdam University Medical Center, Netherlands Barton HAYNES, Duke Human Vaccine Institute and the Center for HIV-AIDS Vaccine Immunology, United States Kevin SAUNDERS, Duke University Medical Center, United States Lynn MORRIS, National Institute for Communicable Diseases, South Africa Glenda GRAY, South African Medical Research Council, South Africa

AUTHOR

Alejandro Balazs

SUMMARY

This session looked at both active immunization and passive infusion as potential strategies for HIV prevention. These included novel vaccines employing peptide-liposomes, mRNA-lipid nanoparticles or SOSIP trimer protein immunogens. Detailed analysis of breakthrough infections observed during the AMP study of VRC01 passive transfer was also highlighted.

HIGHLIGHTS

Bart Haynes showed progress inducing two broadly neutralizing antibodies using a variety of immunogen platforms. He went over advantages of mRNA-based immunogen delivery and their plans to conduct rapid, small-scale immunization studies to iterate vaccine approaches to develop two bNAb lineages starting in 2023 with the goal of inducing these by 2025 and using them as a bivalent vaccine for efficacy studies. Godelieve de Bree presented results from the ACTHIVE-001 study of SOSIP trimer protein demonstrating that it was safe and effective at stimulating autologous neutralizing antibody responses in humans. Kevin Saunders used a novel computational tool (Armadillo) to define the improbable mutations in the germline sequence found in the DH270.6 bNAb lineage which are difficult to elicit through traditional protein-based immunization. However, the use of mRNA-LNPs in mice increased the frequency of these improbable mutations over other immunogens. Lynn Morris showed analysis of breakthrough infections in the AMP study to create a PT80 biomarker defining prevention efficacy against autologous virus. This suggested that 200-fold more antibody is required to prevent transmission in vivo than that measured in vitro. Computational analysis was performed to demonstrate that a combination of three bNAbs could be successful in a future passive transfer study.

CRITICAL ASSESSMENT

mRNA-LNP-based immunogens represent a paradigm shift for future vaccines. There are numerous advantages in performing multiple iterative mRNA-based vaccine studies which have the potential to significantly accelerate existing reverse vaccinology strategies. Successful use of SOSIP trimer as an immunogen in humans will be important for ensuring that future vaccines utilize immunogens representing a native conformation. Lessons learned in the AMP study can be applied towards the design of future passive transfer interventions and define important thresholds to inform the likelihood of achieving vaccine efficacy. Computational predictions suggest a clear path forward for combination passive transfer to succeed for HIV prevention.