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Updated: Jul 15, 2026
Analysis of Simian Immunodeficiency Virus-specific CD8+ T-cells in Rhesus Macaques by Peptide-MHC-I Tetramer Staining
Published on: December 23, 2016
Germline-targeting SOSIP trimer immunization elicits precursor CD4 binding-site targeting broadly neutralizing
Ashley N Nelson1, Xiaoying Shen2, Sravani Vekatayogi2
1Department of Pediatrics, Weill Cornell Medicine; New York, NY, USA.
Insights
A novel vaccine strategy using B cell lineage-designed HIV envelope SOSIPs in infant macaques successfully induced broadly neutralizing antibodies (bnAbs) before adolescence. This early childhood immunization approach shows promise for preventing adolescent HIV infections.
Area of Science:
- Immunology
- Vaccinology
- Virology
Background:
- Adolescent HIV prevention requires vaccines inducing protective immunity before sexual debut.
- Early childhood offers a critical window for HIV immunization due to faster broadly neutralizing antibody (bnAb) development in children.
- This study aimed to evaluate a B cell lineage-designed HIV envelope SOSIP vaccine for its ability to induce bnAbs in early life.
Approach:
- Infant rhesus macaques received either BG505 SOSIP or germline-targeting BG505 GT1.1 SOSIP with 3M-052-SE adjuvant at 0, 6, and 12 weeks.
- A pediatric immunization schedule involved boosting all infants with BG505 SOSIP at weeks 26, 52, and 78.
- The study assessed binding antibodies, plasma neutralization, and bnAb precursor development.
Key Points:
- Both immunization strategies elicited durable, high-magnitude binding antibodies and autologous virus neutralization targeting CD4-binding site (CD4bs) or C3/465 epitopes.
- BG505 GT1.1 SOSIP immunization in infants led to neutralization signatures indicative of VRC01-like CD4bs bnAb precursor development and heterologous neutralization.
- Infant rhesus macaques demonstrated precursor bnAb responses at frequencies comparable to adult macaques.
Conclusions:
- A multi-dose immunization regimen with bnAb lineage-designed SOSIPs is a promising strategy for inducing protective HIV bnAb responses in childhood.
- This approach aims to establish protective immunity prior to adolescence, the period of highest HIV exposure risk.
- Early childhood immunization represents a viable window for eliciting potent HIV-specific immune responses.
Abstract:
A vaccine that can achieve protective immunity prior to sexual debut is critical to prevent the estimated 410,000 new HIV infections that occur yearly in adolescents. As children living with HIV can make broadly neutralizing antibody (bnAb) responses in plasma at a faster rate than adults, early childhood is an opportune window for implementation of a multi-dose HIV immunization strategy to elicit protective immunity prior to adolescence. Therefore, the goal of our study was to assess the ability of a B cell lineage-designed HIV envelope SOSIP to induce bnAbs in early life. Infant rhesus macaques (RMs) received either BG505 SOSIP or the germline-targeting BG505 GT1.1 SOSIP (n=5/group) with the 3M-052-SE adjuvant at 0, 6, and 12 weeks of age. All infant RMs were then boosted with the BG505 SOSIP at weeks 26, 52 and 78, mimicking a pediatric immunization schedule of multiple vaccine boosts within the first two years of life. Both immunization strategies induced durable, high magnitude binding antibodies and plasma autologous virus neutralization that primarily targeted the CD4-binding site (CD4bs) or C3/465 epitope. Notably, three BG505 GT1.1-immunized infants exhibited a plasma HIV neutralization signature reflective of VRC01-like CD4bs bnAb precursor development and heterologous virus neutralization. Finally, infant RMs developed precursor bnAb responses at a similar frequency to that of adult RMs receiving a similar immunization strategy. Thus, a multi-dose immunization regimen with bnAb lineage designed SOSIPs is a promising strategy for inducing protective HIV bnAb responses in childhood prior to adolescence when sexual HIV exposure risk begins.
