Antibody responses induced by SHIV infection are more focused than those induced by soluble native HIV-1 envelope trimers in non-human primates.

TitleAntibody responses induced by SHIV infection are more focused than those induced by soluble native HIV-1 envelope trimers in non-human primates.
Publication TypeJournal Article
Year of Publication2021
Authorsvan Schooten J, van Haaren MM, Li H, McCoy LE, Havenar-Daughton C, Cottrell CA, Burger JA, van der Woude P, Helgers LC, Tomris I, LaBranche CC, Montefiori DC, Ward AB, Burton DR, Moore JP, Sanders RW, Crotty S, Shaw GM, van Gils MJ
JournalPLoS Pathog
Volume17
Issue8
Paginatione1009736
Date Published2021 Aug
ISSN1553-7374
KeywordsAIDS Vaccines, Animals, Antibodies, Monoclonal, Antibodies, Neutralizing, Antibody Formation, Antigens, Viral, env Gene Products, Human Immunodeficiency Virus, Epitopes, HIV Antibodies, HIV Infections, HIV-1, Humans, Immunization, Infant, Kenya, Primates, Protein Multimerization, Simian Acquired Immunodeficiency Syndrome, Simian immunodeficiency virus, Vaccination
Abstract

The development of an effective human immunodeficiency virus (HIV-1) vaccine is a high global health priority. Soluble native-like HIV-1 envelope glycoprotein trimers (Env), including those based on the SOSIP design, have shown promise as vaccine candidates by inducing neutralizing antibody responses against the autologous virus in animal models. However, to overcome HIV-1's extreme diversity a vaccine needs to induce broadly neutralizing antibodies (bNAbs). Such bNAbs can protect non-human primates (NHPs) and humans from infection. The prototypic BG505 SOSIP.664 immunogen is based on the BG505 env sequence isolated from an HIV-1-infected infant from Kenya who developed a bNAb response. Studying bNAb development during natural HIV-1 infection can inform vaccine design, however, it is unclear to what extent vaccine-induced antibody responses to Env are comparable to those induced by natural infection. Here, we compared Env antibody responses in BG505 SOSIP-immunized NHPs with those in BG505 SHIV-infected NHPs, by analyzing monoclonal antibodies (mAbs). We observed three major differences between BG505 SOSIP immunization and BG505 SHIV infection. First, SHIV infection resulted in more clonal expansion and less antibody diversity compared to SOSIP immunization, likely because of higher and/or prolonged antigenic stimulation and increased antigen diversity during infection. Second, while we retrieved comparatively fewer neutralizing mAbs (NAbs) from SOSIP-immunized animals, these NAbs targeted more diverse epitopes compared to NAbs from SHIV-infected animals. However, none of the NAbs, either elicited by vaccination or infection, showed any breadth. Finally, SOSIP immunization elicited antibodies against the base of the trimer, while infection did not, consistent with the base being placed onto the virus membrane in the latter setting. Together these data provide new insights into the antibody response against BG505 Env during infection and immunization and limitations that need to be overcome to induce better responses after vaccination.

DOI10.1371/journal.ppat.1009736
Alternate JournalPLoS Pathog
PubMed ID34432859
PubMed Central IDPMC8423243
Grant ListUM1 AI144462 / AI / NIAID NIH HHS / United States
UM1 AI100663 / AI / NIAID NIH HHS / United States
R61 AI161818 / AI / NIAID NIH HHS / United States
R01 AI036082 / AI / NIAID NIH HHS / United States
R01 AI165080 / AI / NIAID NIH HHS / United States
P01 AI110657 / AI / NIAID NIH HHS / United States
R01 AI131331 / AI / NIAID NIH HHS / United States
R01 AI160607 / AI / NIAID NIH HHS / United States
P01 AI131251 / AI / NIAID NIH HHS / United States
F31 AI131873 / AI / NIAID NIH HHS / United States

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