Skip to main content

A neutralizing antibody target in early HIV-1 infection was recapitulated in rhesus macaques immunized with the transmitted/founder envelope sequence.

Publication ,  Journal Article
Welbourn, S; Chakraborty, S; Yang, JE; Gleinich, AS; Gangadhara, S; Khan, S; Ferrebee, C; Yagnik, B; Burton, S; Charles, T; Smith, SA; Wang, S ...
Published in: PLoS Pathog
May 2022

Transmitted/founder (T/F) HIV-1 envelope proteins (Envs) from infected individuals that developed neutralization breadth are likely to possess inherent features desirable for vaccine immunogen design. To explore this premise, we conducted an immunization study in rhesus macaques (RM) using T/F Env sequences from two human subjects, one of whom developed potent and broad neutralizing antibodies (Z1800M) while the other developed little to no neutralizing antibody responses (R66M) during HIV-1 infection. Using a DNA/MVA/protein immunization protocol, 10 RM were immunized with each T/F Env. Within each T/F Env group, the protein boosts were administered as either monomeric gp120 or stabilized trimeric gp140 protein. All vaccination regimens elicited high titers of antigen-specific IgG, and two animals that received monomeric Z1800M Env gp120 developed autologous neutralizing activity. Using early Env escape variants isolated from subject Z1800M as guides, the serum neutralizing activity of the two immunized RM was found to be dependent on the gp120 V5 region. Interestingly, the exact same residues of V5 were also targeted by a neutralizing monoclonal antibody (nmAb) isolated from the subject Z1800M early in infection. Glycan profiling and computational modeling of the Z1800M Env gp120 immunogen provided further evidence that the V5 loop is exposed in this T/F Env and was a dominant feature that drove neutralizing antibody targeting during infection and immunization. An expanded B cell clonotype was isolated from one of the neutralization-positive RM and nmAbs corresponding to this group demonstrated V5-dependent neutralization similar to both the RM serum and the human Z1800M nmAb. The results demonstrate that neutralizing antibody responses elicited by the Z1800M T/F Env in RM converged with those in the HIV-1 infected human subject, illustrating the potential of using immunogens based on this or other T/F Envs with well-defined immunogenicity as a starting point to drive breadth.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

PLoS Pathog

DOI

EISSN

1553-7374

Publication Date

May 2022

Volume

18

Issue

5

Start / End Page

e1010488

Location

United States

Related Subject Headings

  • env Gene Products, Human Immunodeficiency Virus
  • Virology
  • Macaca mulatta
  • Humans
  • HIV-1
  • HIV Infections
  • HIV Envelope Protein gp120
  • HIV Antibodies
  • Antibodies, Neutralizing
  • Animals
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Welbourn, S., Chakraborty, S., Yang, J. E., Gleinich, A. S., Gangadhara, S., Khan, S., … Derdeyn, C. A. (2022). A neutralizing antibody target in early HIV-1 infection was recapitulated in rhesus macaques immunized with the transmitted/founder envelope sequence. PLoS Pathog, 18(5), e1010488. https://doi.org/10.1371/journal.ppat.1010488
Welbourn, Sarah, Srirupa Chakraborty, Jie E. Yang, Anne S. Gleinich, Sailaja Gangadhara, Salar Khan, Courtney Ferrebee, et al. “A neutralizing antibody target in early HIV-1 infection was recapitulated in rhesus macaques immunized with the transmitted/founder envelope sequence.PLoS Pathog 18, no. 5 (May 2022): e1010488. https://doi.org/10.1371/journal.ppat.1010488.
Welbourn S, Chakraborty S, Yang JE, Gleinich AS, Gangadhara S, Khan S, et al. A neutralizing antibody target in early HIV-1 infection was recapitulated in rhesus macaques immunized with the transmitted/founder envelope sequence. PLoS Pathog. 2022 May;18(5):e1010488.
Welbourn, Sarah, et al. “A neutralizing antibody target in early HIV-1 infection was recapitulated in rhesus macaques immunized with the transmitted/founder envelope sequence.PLoS Pathog, vol. 18, no. 5, May 2022, p. e1010488. Pubmed, doi:10.1371/journal.ppat.1010488.
Welbourn S, Chakraborty S, Yang JE, Gleinich AS, Gangadhara S, Khan S, Ferrebee C, Yagnik B, Burton S, Charles T, Smith SA, Williams D, Mopuri R, Upadhyay AA, Thompson J, Price MA, Wang S, Qin Z, Shen X, Williams LD, Eisel N, Peters T, Zhang L, Kilembe W, Karita E, Tomaras GD, Bosinger SE, Amara RR, Azadi P, Wright ER, Gnanakaran S, Derdeyn CA. A neutralizing antibody target in early HIV-1 infection was recapitulated in rhesus macaques immunized with the transmitted/founder envelope sequence. PLoS Pathog. 2022 May;18(5):e1010488.

Published In

PLoS Pathog

DOI

EISSN

1553-7374

Publication Date

May 2022

Volume

18

Issue

5

Start / End Page

e1010488

Location

United States

Related Subject Headings

  • env Gene Products, Human Immunodeficiency Virus
  • Virology
  • Macaca mulatta
  • Humans
  • HIV-1
  • HIV Infections
  • HIV Envelope Protein gp120
  • HIV Antibodies
  • Antibodies, Neutralizing
  • Animals