BG505 GT1.1 gp140 adjuvanted / GSK, IAVI, Rockefeller University - LARVOL DELTA

Germline-targeting HIV Envelope SOSIP immunization more frequently elicits broadly-neutralizing antibody precursor responses in infant compared to juvenile rhesus macaques. (PubMed, bioRxiv) - "Animals received 3 doses of the germline-targeting BG505 GT1.1 immunogen, followed by 3 boosts of wild-type BG505 SOSIP, each adjuvanted with the TLR7/8 agonist, 3M-052-SE...Finally, administration of the mixed clade B nanoparticle was able to increase the breadth of antibody responses in 3 of 5 infants and 2 of 4 juveniles. These results suggest that immunization in early-life may enhance bnAb induction and highlight the potential for future pediatric HIV-1 vaccine strategies."

Journal • Human Immunodeficiency Virus • Infectious Disease • Pediatrics • CD4

Germline-Targeting SOSIP Trimer Immunizations Reduced Post-Rebound SHIV Loads in Infant Macaques (CROI 2025) - "Of these, 5 RMs were immunized with 4 doses of BG505 GT1.1 SOSIP+3M052-SE, followed by 3 doses of autologous SF162P3 SOSIP+3M052-SE, and 6 RMs did not receive any immunizations (controls). Importantly, none of the controls and 2/5 immunized animals developed VRC01-class bNAb precursor response, and the RM with the highest level of autologous virus-neutralizing antibody at 2 weeks post-ATI did not experience viral rebound. Conclusions Germline-targeting native-like HIV env trimer immunization of SHIV-infected infant RMs, induced potent HIV-specific antibody levels and CD4bs-specific bNAb precursor response resulting in dampened viral replication for 15 weeks post-ATI."

Human Immunodeficiency Virus • Infectious Disease • Pediatrics

Enhanced HIV Antibody Precursor Development With Early-Life Germline Targeting Immunization (CROI 2025) - "Methods Infant (n=5) and juvenile (n=4) RMs received 3 immunizations of the germline-targeting BG505 GT1.1 SOSIP trimer (50mg) with the 3M-052-SE adjuvant 6 weeks apart...Conclusions Our data indicates that sequential immunization with germline-targeting BG505 SOSIP trimers may elicit CD4bs bnAb precursors more frequently in infants compared to juveniles. Our results highlight the potential for an HIV immunization strategy in early life to induce protective bnAb responses and can inform future human pediatric clinical trials."

Human Immunodeficiency Virus • Infectious Disease • Pediatrics • CD4

Immunogenicity of HIV BG505 germline-targeting GT1.1 SOSIP envelope trimer immunization in infant and juvenile rhesus macaques (HIVR4P 2024) - "In this study we compared the ability of a CD4 binding site (CD4bs) germline-targeting SOSIP trimer immunization strategy to induce precursor bnAbs in infant and juvenile rhesus macaques (RMs). Infant (n=5) and juvenile (n=4) RMs received 3 immunizations of the germline-targeting BG505 GT1.1 SOSIP trimer (50ug) with the 3M-052-SE adjuvant 6 weeks apart... Our data indicates that sequential immunization with germline-targeting BG505 SOSIP trimers may induce neutralizing antibodies and CD4bs bnAb precursors more frequently in infant compared to juvenile. Our results highlight the potential for an HIV immunization strategy in early life to induce protective bnAb responses and can inform approaches for future human pediatric clinical trials."

Human Immunodeficiency Virus • Infectious Disease • Pediatrics • CD4

Induction of precursor CD4 binding-site targeting broadly neutralizing antibodies in infant macaques following immunization with germline-targeting SOSIP trimers (HIVR4P 2024) - "As the elicitation of bnAbs will be critical for an effective HIV vaccine, the goal of our study was to assess the ability of a B cell lineage-designed HIV envelope SOSIP to induce precursor CD4bs-targeting bnAbs in early life. Infant rhesus macaques (RMs) received either the wild-type (WT) BG505 SOSIP or the CD4bs germline-targeting BG505 GT1.1 SOSIP (n=5/group) with the 3M-052-SE adjuvant at 0, 6, and 12 weeks of age...Most notably, three GT1.1-primed infants exhibited a plasma HIV neutralization signature reflective of VRC01-like CD4bs bnAb precursor development... Thus, a multi-dose immunization regimen with bnAb lineage designed SOSIPs is a promising strategy for implementation in early childhood, and the induction of early B cell responses with the potential to mature into protective HIV bnAbs prior to adolescence when sexual HIV exposure risk begins."

Human Immunodeficiency Virus • Infectious Disease • Pediatrics • CD4

A comparison of humoral immune responses induced by infant HIV BG505 germline-targeting SOSIP envelope trimer vaccination across immunogen platforms (HIVR4P 2024) - "All groups received a booster of either BG505.GT1.1 SOSIP or BG505.664 SOSIP at weeks 24 or 26, 52, and 78. Across platforms, BG505 GT1.1 SOSIP trimer protein immunization elicited higher plasma IgG binding responses following the 2nd immunization compared to the mRNA-immunized RMs... While our data suggests that protein-based priming immunization with germline-targeting SOSIP trimers may induce higher-magnitude vaccine-specific antibodies and induce CD4bs bnAb precursors at a higher rate than sequence-matched mRNA-based vaccination in early life, a new antigen design could better harness the advantages of mRNA and produce more optimal results. Future work will include the optimization of intermediate immunogens that can facilitate the maturation of development of bnAb B cell lineages initiated by GT immunogens."

Human Immunodeficiency Virus • Infectious Disease • CD4

GERMLINE-TARGETING ENV TRIMER ELICITS bNAb PRECURSORS IN INFANT, NOT JUVENILE MONKEYS (CROI 2023) - " Infant (n=5) and juvenile (n=4) rhesus macaques (RMs) received 3 immunizations of the germline-targeting BG505 GT1.1 SOSIP trimer (50mg) with the 3M-052-SE adjuvant 6 weeks apart... Our data demonstrates that sequential immunization of infant RMs with germline-targeting and wildtype BG505 SOSIP trimers can induce high serum neutralizing antibody titers and CD4bs bnAb precursors, while these responses were not detectable in vaccinated juvenile RMs. Our results support observations in human studies suggesting that the infant immune environment is better suited for induction of plasma HIV bnAb responses."

Late-breaking abstract • Human Immunodeficiency Virus • Infectious Disease • CD4