Immunization with germ line-targeting SOSIP trimers elicits broadly neutralizing antibody precursors in infant macaques.

TitleImmunization with germ line-targeting SOSIP trimers elicits broadly neutralizing antibody precursors in infant macaques.
Publication TypeJournal Article
Year of Publication2024
AuthorsNelson AN, Shen X, Vekatayogi S, Zhang S, Ozorowski G, Dennis M, Sewall LM, Milligan E, Davis D, Cross KA, Chen Y, van Schooten J, Eudailey J, Isaac J, Memon S, Weinbaum C, Gao H, Stanfield-Oakley S, Byrd A, Chutkan S, Berendam S, Cronin K, Yasmeen A, Alam S, LaBranche CC, Rogers K, Shirreff L, Cupo A, Derking R, Villinger F, Klasse PJohan, Ferrari G, Williams WB, Hudgens MG, Ward AB, Montefiori DC, Van Rompay KKA, Wiehe K, Moore JP, Sanders RW, De Paris K, Permar SR
JournalSci Immunol
Volume9
Issue98
Paginationeadm7097
Date Published2024 Aug 30
ISSN2470-9468
KeywordsAIDS Vaccines, Animals, Antibodies, Neutralizing, Broadly Neutralizing Antibodies, env Gene Products, Human Immunodeficiency Virus, Germ Cells, HIV Antibodies, HIV Infections, HIV-1, Humans, Immunization, Macaca mulatta
Abstract

Adolescents are a growing population of people living with HIV. The period between weaning and sexual debut presents a low-risk window for HIV acquisition, making early childhood an ideal time for implementing an immunization regimen. Because the elicitation of broadly neutralizing antibodies (bnAbs) is critical for an effective HIV vaccine, our goal was to assess the ability of a bnAb B cell lineage-designed HIV envelope SOSIP (protein stabilized by a disulfide bond between gp120-gp41-named "SOS"-and an isoleucine-to-proline point mutation-named "IP"-at residue 559) to induce precursor CD4 binding site (CD4bs)-targeting bnAbs in early life. Infant rhesus macaques received either a BG505 SOSIP, based on the infant BG505 transmitted/founder virus, or the CD4bs germ line-targeting BG505 SOSIP GT1.1 (n = 5 per group). Although both strategies induced durable, high-magnitude plasma autologous virus neutralization responses, only GT1.1-immunized infants (n = 3 of 5) exhibited VRC01-like CD4bs bnAb precursor development. Thus, a multidose immunization regimen with bnAb lineage-designed SOSIPs shows promise for inducing early B cell responses with the potential to mature into protective HIV bnAbs before sexual debut.

DOI10.1126/sciimmunol.adm7097
Alternate JournalSci Immunol
PubMed ID39213340
PubMed Central IDPMC12302664
Grant ListHHSN272201800004C / AI / NIAID NIH HHS / United States
T32 ES007018 / ES / NIEHS NIH HHS / United States
P51 OD011107 / OD / NIH HHS / United States
P30 CA016086 / CA / NCI NIH HHS / United States
P01 AI110657 / AI / NIAID NIH HHS / United States
P30 AI050410 / AI / NIAID NIH HHS / United States
KL2 TR002385 / TR / NCATS NIH HHS / United States
P01 AI117915 / AI / NIAID NIH HHS / United States

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