IAS 2023: bNAbs for prevention and cure: antiviral and vaccine-like responses

1 October 2023. Related: Conference reports, Antiretrovirals, HIV prevention and transmission, Cure-related research, Vaccines and microbicides, IAS 2023 Brisbane.

Kirk Taylor and Simon Collins, HIV i-Base

IAS 2023 included many presentations that reviewed the different ways that broadly neutralising antibodies (bNAbs) are being used in prevention and treatment studies, many of which are now available as webcasts.

These made up for the few clinical studies.

Duration of antiviral effect of 3BNC117 and 10-1074

IAS 2023 included a PK study that modelled the maximum time that a single dose of two broadly neutralising antibodies (bNAbs) would be expected to have antiviral activity. [1]

This is relevant for cure-related research such as the RIO study which involves interrupting ART to see how long viral load remains suppressed due to these bNAbs. [2]

The bNAbs 3BNC117 (TAB; teropavimab) and 10-1074 (ZAB; zinlirvimab) bind to distinct regions of the HIV envelope. bNAb infusion leads to rapid reduction of viral load and delay of viral rebound for people with an undetectable viral load.

A pharmacokinetic (PK) model was generated with data points (n=265) from six efficacy studies conducted in people living with HIV and three PK studies. Estimated half-lives were longer in people who had undetectable vs detectable viral load for both 3BNC117 (62 vs 46 days) and 10-1074 (79 vs 55 days).

The poster concluded that these data suggest that a 48-week washout period after bNAb infusion is required to evaluate their efficacy in HIV cure studies.

Despite this modelling, cases have been reported where viral suppression is maintained for longer than a year, and after bNAb concentrations are no longer detected or active, suggesting that in addition to antiviral properties, bNAbs might induce through the FC domains a vaccine-like effect. [3]

Vaccine-like properties of bNAbs

The evidence for a vaccine effect, both anti-viral and anti-tumour, was discussed in more detail by Carey Hwang in a satellite meeting on the development of bNAbs for prevention and cure, organised by IAS and available as a webcast. [4, 5]

bNabs for prevention, vaccine and cure

Another IAS satellite, organised with IAVI, looked at the potential for bNAbs used as post-natal prophylaxis for infants. [6]

In the main conference programme, Wilton Williams and Katharine Bar reviewed bNAbs research for an HIV vaccine and cure, respectively, and although the slides are available online, these talks do not seem to be webcast. [7, 8]

IAS 2023 also included an oral presentation and e-poster on bNAb studies conducted in non-human primates and methods for bNAb production. [9, 10]

comment

3BNC117 and 10-1074 were both developed by Michel Nussenzweig and colleagues at Rockefeller University and were licensed to Gilead Sciences in January 2020. [11]

The RIO study is still currently enrolling in the UK. [2]

References

Unless stated otherwise, all references are to the Programme and Abstracts of the 12th IAS conference (IAS 2023), 23–26 July 2023, Brisbane, Australia.

1. Zheng Y et al. Evaluation of therapeutic concentrations of anti-HIV antibodies 3BNC117/teropavimab and 10-1074/zinlirvirmab through PK-PD modelling and prediction of the washout duration in HIV cure studies. IAS 2023, 23–26 July 2023, Brisbane, Australia. Poster abstract TUPEB05.
   https://programme.ias2023.org/Abstract/Abstract/?abstractid=4615 (abstract)
2. The RIO study.
   https://riotrial.org
3. Collins S. bNAb research at CROI 2019: vaccine, prevention, treatment and cure… HTB (April 2019)
   https://i-base.info/htb/36040
4. Hwang C. bnAbs vaccinal effect – preclinical data and models. IAS 2023, SAT054.
   https://programme.ias2023.org/Programme/Session/4387
5. IAS Satellite. bnAbs: From prevention to cure. SAT054.
   https://programme.ias2023.org/Programme/Session/4387
6. IAS Satellite. The promise of bnAbs for infant post-natal prophylaxis to end paediatric HIV: the path forward. IAS 2023, SAT029.
   https://programme.ias2023.org/Programme/Session/4390
7. Williams W. Engineered HIV-1 immunogens to induce bNAb responses. IAS 2023, Plenary lecture PL01.
   https://programme.ias2023.org/Programme/Session/4365
8. Bar K. Strategies for using antibodies for HIV cure. IAS 2023, Plenary lecture PL01.
   https://programme.ias2023.org/Programme/Session/4365
9. Solis Leal A et al. Effect of combination latency reversing agents and bNAb in SHIV-infected rhesus macaques on antiretroviral therapy. IAS 2023, 23–26 July 2023, Brisbane, Australia. E Poster abstract EPA0080.
10. Chen X et al. Diverse envelope trimers with altered glycan coverage around the CD4-binding site elicit neutralizing antibodies of >50% breadth in NHPs. . IAS 2023, 23–26 July 2023, Brisbane, Australia. Oral abstract OAA0404.
11. Gilead Sciences. Gilead Sciences Licenses Portfolio of HIV Antibodies From The Rockefeller University. (9 January 2020).
    https://www.gilead.com/news-and-press/press-room/press-releases/2020/1/gilead-sciences-licenses-portfolio-of-hiv-antibodies-from-the-rockefeller-university