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A novel HIV triple broadly neutralizing antibody (bNAb) combination-based passive immunization of infant rhesus macaques achieves durable protective plasma neutralization levels and mediates anti-viral effector functions.

Publication ,  Journal Article
Dankwa, S; Kosman, C; Dennis, M; Giorgi, EE; Vuong, K; Pahountis, I; Garza, A; Binuya, C; McCarthy, J; Mayer, BT; Ngo, JT; Enemuo, CA ...
Published in: PLoS One
2024

To eliminate vertical HIV transmission and achieve therapy-free viral suppression among children living with HIV, novel strategies beyond antiretroviral therapy (ART) are necessary. Our group previously identified a triple broadly neutralizing antibody (bNAb) combination comprising of 3BNC117, PGDM1400 and PGT151 that mediates robust in vitro neutralization and non-neutralizing effector functions against a cross-clade panel of simian human immunodeficiency viruses (SHIVs). In this study, we evaluated the safety, pharmacokinetics, and antiviral potency of this bNAb combination in infant rhesus macaques (RMs). We demonstrate that subcutaneous infusion of the triple bNAb regimen was well tolerated in pediatric monkeys and resulted in durable systemic and mucosal distribution. Plasma obtained from passively-immunized RMs demonstrated potent HIV-neutralizing and Fc-mediated antiviral effector functions. Finally, using the predicted serum neutralization 80% inhibitory dilution titer (PT80) biomarker threshold of >200, which was recently identified as a surrogate endpoint for evaluation of the preventative efficacy of bNAbs against mucosal viral acquisition in human clinical trials, we demonstrated that our regimen has PT80>200 against a large panel of plasma and breast milk-derived HIV strains and cross-clade SHIV variants. This data will guide the development of combination bNAbs for eliminating vertical HIV transmission and for achieving ART-free viral suppression among children living with HIV.

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Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2024

Volume

19

Issue

11

Start / End Page

e0312411

Location

United States

Related Subject Headings

  • Simian immunodeficiency virus
  • Simian Immunodeficiency Virus
  • Simian Acquired Immunodeficiency Syndrome
  • Macaca mulatta
  • Immunization, Passive
  • Humans
  • HIV-1
  • HIV Infections
  • HIV Antibodies
  • General Science & Technology
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Dankwa, S., Kosman, C., Dennis, M., Giorgi, E. E., Vuong, K., Pahountis, I., … Goswami, R. (2024). A novel HIV triple broadly neutralizing antibody (bNAb) combination-based passive immunization of infant rhesus macaques achieves durable protective plasma neutralization levels and mediates anti-viral effector functions. PLoS One, 19(11), e0312411. https://doi.org/10.1371/journal.pone.0312411
Dankwa, Sedem, Christina Kosman, Maria Dennis, Elena E. Giorgi, Kenneth Vuong, Ioanna Pahountis, Ashley Garza, et al. “A novel HIV triple broadly neutralizing antibody (bNAb) combination-based passive immunization of infant rhesus macaques achieves durable protective plasma neutralization levels and mediates anti-viral effector functions.PLoS One 19, no. 11 (2024): e0312411. https://doi.org/10.1371/journal.pone.0312411.
Dankwa S, Kosman C, Dennis M, Giorgi EE, Vuong K, Pahountis I, Garza A, Binuya C, McCarthy J, Mayer BT, Ngo JT, Enemuo CA, Carnathan DG, Stanfield-Oakley S, Berendam SJ, Weinbaum C, Engelman K, Magnani DM, Chan C, Ferrari G, Silvestri G, Amara RR, Chahroudi A, Permar SR, Fouda GG, Goswami R. A novel HIV triple broadly neutralizing antibody (bNAb) combination-based passive immunization of infant rhesus macaques achieves durable protective plasma neutralization levels and mediates anti-viral effector functions. PLoS One. 2024;19(11):e0312411.

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2024

Volume

19

Issue

11

Start / End Page

e0312411

Location

United States

Related Subject Headings

  • Simian immunodeficiency virus
  • Simian Immunodeficiency Virus
  • Simian Acquired Immunodeficiency Syndrome
  • Macaca mulatta
  • Immunization, Passive
  • Humans
  • HIV-1
  • HIV Infections
  • HIV Antibodies
  • General Science & Technology