BG505 SOSIP 664 gp140 adjuvanted vaccine / GSK, IAVI - LARVOL DELTA

Evaluating the Safety and Immunogenicity of HIV-1 BG505 SOSIP.664 gp140 With TLR Agonist and/or Alum Adjuvants in Healthy, HIV-uninfected Adults (clinicaltrials.gov) - P1 | N=127 | Completed | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Active, not recruiting ➔ Completed

Trial completion • Human Immunodeficiency Virus • Infectious Disease

HIV BG505 SOSIP.664 trimer with 3M-052-AF/alum induces broad and potent ADCC-mediating antibodies (HIVR4P 2024) - "HVTN 137-Part B is a phase 1 clinical trial to evaluate the immunogenicity of the HIV-1 subtype A stabilized trimer, BG505 SOSIP.664 gp140, in combination with different adjuvants: the TLR9 agonist CpG 1018, the TLR7/8 agonist 3M-052-AF, both given with Alum, the TLR4 agonist GLA-LSQ, or Alum alone. 3M-052-AF+Alum represents a potent adjuvant that can elicit broad ADCC responses in addition to neutralizing responses and represents a strong candidate for use in future HIV vaccine trials."

Late-breaking abstract • Human Immunodeficiency Virus • Infectious Disease • TLR4

HIV BG505 SOSIP.664 trimer with 3M-052-AF+alum induces a lasting IFN signature that correlates with the development of HIV-1 antibodies (HIVR4P 2024) - "BACKGROUND: HVTN137 is a phase 1 trial evaluating the safety and immunogenicity of HIV-1 BG505 SOSIP.664 gp140 (BG505SOSIP), a stable soluble envelope, with distinct adjuvant formulations, including 5mcg of TLR7/8 adjuvant 3M-052-AF+alum, and alum alone... IFN signaling pathways in blood of BG505SOSIP+3M-052-AF+alum vaccinees peaked 1-3 days post-immunization, and mostly returned to baseline by 2.5WPTV. However, both in blood and rectal tissue, a subset of type I IFN DEGs persisted only in BG505SOSIP+3M-052-AF+alum vaccinees, indicating a 2.5-week-long TLR7/8 response in blood and mucosa. This IFN signature in blood correlated with BG505SOSIP bAbs, suggesting it may support the development of a strong B cell response."

Late-breaking abstract • Human Immunodeficiency Virus • Infectious Disease • CD4 • CD86 • IFIT1 • MX1 • TLR7 • TRIM6

BG505 SOSIP.664 adjuvanted with 3M-052 tunes IgG Fc glycosylation towards a more functional state (HIVR4P 2024) - "This study aimed to measure the impact of vaccine adjuvants on glycosylation and FcmEF to understand potentially programmable antibody features for future vaccine designs. HVTN 137 enrolled US adults without HIV (n=70) for a Phase 1 study evaluating an HIV-1 vaccine candidate featuring BG505 SOSIP.664gp140. Each group received a distinct adjuvant: CpG1018-Alum, 3M-052-AF-Alum, GLA-LSQ, or Alum... 3M-052-AF-Alum elicited the most functional antibody response evidenced by increased ADCP and ADCD post-vaccination three. Antibodies generated post-vaccination two lacking effector functions suggests qualitative tuning of the response. Our data suggest increased Fc galactosylation and fucosylation and decreased sialylation could contribute to increased phagocytic function and can be tuned by adjuvant selection."

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

Use of 3M-052-AF with Alum adjuvant in HIV trimer vaccine induces human autologous neutralizing antibodies. (PubMed, J Exp Med) - "We evaluated trimeric BG505 SOSIP.664 gp140 formulated with a novel TLR7/8 signaling adjuvant, 3M-052-AF/Alum, for safety, adjuvant dose-finding, and immunogenicity in a first-in-healthy adult (n = 17), randomized, and placebo-controlled trial (HVTN 137A)...Trimer-specific, B cell-derived monoclonal antibody activities confirmed these results and showed weak heterologous neutralization in the strongest responder. Our findings demonstrate the clinical utility of the 3M-052-AF/Alum adjuvant and support further improvements of trimer-based Env immunogens to focus responses on multiple broad nAb epitopes."

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

A Study to Evaluate the Safety and Immunogenicity of 2 Doses of 100µg BG505 SOSIP.664 gp140 Vaccine, Adjuvanted, Given to a Population of Adults Who Have Received 3 Doses of 300µg BG505 SOSIP.GT1.1 gp140 Vaccine, Adjuvanted (clinicaltrials.gov) - P1 | N=8 | Enrolling by invitation | Sponsor: International AIDS Vaccine Initiative | Not yet recruiting ➔ Enrolling by invitation | Initiation date: Nov 2023 ➔ Apr 2024 | Trial primary completion date: Mar 2024 ➔ Mar 2025

Enrollment open • Trial initiation date • Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease

A Randomized, Double-blinded, Placebo-controlled, Dose-escalation Phase 1 Clinical Trial to Evaluate the Safety and Immunogenicity of Recombinant HIV Envelope Protein BG505 SOSIP.664 gp140 Vaccine, Adjuvanted, in Healthy, HIV-1 Uninfected Adults (clinicaltrials.gov) - P1 | N=61 | Completed | Sponsor: International AIDS Vaccine Initiative | Active, not recruiting ➔ Completed

Trial completion • Human Immunodeficiency Virus • Infectious Disease

A Study to Evaluate the Safety and Immunogenicity of 2 Doses of 100µg BG505 SOSIP.664 gp140 Vaccine, Adjuvanted, Given to a Population of Adults Who Have Received 3 Doses of 300µg BG505 SOSIP.GT1.1 gp140 Vaccine, Adjuvanted (clinicaltrials.gov) - P1 | N=8 | Not yet recruiting | Sponsor: International AIDS Vaccine Initiative

New P1 trial • Human Immunodeficiency Virus • Infectious Disease

Evaluating the Safety and Immunogenicity of HIV-1 BG505 SOSIP.664 gp140 With TLR Agonist and/or Alum Adjuvants in Healthy, HIV-uninfected Adults (clinicaltrials.gov) - P1 | N=127 | Active, not recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Trial completion date: Jul 2023 ➔ Nov 2024 | Trial primary completion date: Jul 2023 ➔ Nov 2024

Trial completion date • Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease • CD4

Evaluating the Safety and Immunogenicity of HIV-1 BG505 SOSIP.664 gp140 With TLR Agonist and/or Alum Adjuvants in Healthy, HIV-uninfected Adults (clinicaltrials.gov) - P1 | N=127 | Active, not recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Recruiting ➔ Active, not recruiting

Enrollment closed • Human Immunodeficiency Virus • Infectious Disease • CD4

A Clinical Trial to Evaluate the Safety and Immunogenicity of a Prophylactic HIV Vaccine Candidate (clinicaltrials.gov) - P1 | N=14 | Not yet recruiting | Sponsor: International AIDS Vaccine Initiative

New P1 trial • Human Immunodeficiency Virus • Infectious Disease

Evaluating the Safety and Immunogenicity of HIV-1 BG505 SOSIP.664 gp140 With TLR Agonist and/or Alum Adjuvants in Healthy, HIV-uninfected Adults (clinicaltrials.gov) - P1 | N=105 | Recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Trial completion date: May 2022 ➔ Jul 2023 | Trial primary completion date: May 2022 ➔ Apr 2023

Trial completion date • Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease • CD4

Enhanced HIV SOSIP Envelope yields in plants through transient co-expression of peptidyl-prolyl isomerase B and calreticulin chaperones and ER targeting. (PubMed, Sci Rep) - "The present study utilized the Nicotiana benthamiana/p19 (N.b./p19) transient plant system to assess co-expression of two ER master regulators and 5 chaperones, crucial in the folding process, to enhance yields of three Env SOSIPs, single chain BG505 SOSIP.664 gp140, CH505TF.6R.SOSIP.664.v4.1 and CH848-10.17-DT9...Results are consistent with reducing SOSIP misfolding and cellular stress due to increased exposure to the plant host cell's calnexin/calreticulin network and accelerating the rate-limiting cis-trans isomerization of Xaa-Pro peptide bonds respectively. Plant transient co-expression facilitates rapid identification of host cell factors and will be translatable to other complex glycoproteins and mammalian expression systems."

Journal • Human Immunodeficiency Virus • Infectious Disease • CALR

A Randomized, Double-blinded, Placebo-controlled, Dose-escalation Phase 1 Clinical Trial to Evaluate the Safety and Immunogenicity of Recombinant HIV Envelope Protein BG505 SOSIP.664 gp140 Vaccine, Adjuvanted, in Healthy, HIV-1 Uninfected Adults (clinicaltrials.gov) - P1 | N=61 | Active, not recruiting | Sponsor: International AIDS Vaccine Initiative | Recruiting ➔ Active, not recruiting | Trial completion date: May 2020 ➔ Aug 2023 | Trial primary completion date: May 2020 ➔ Mar 2023

Enrollment closed • Trial completion date • Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease

[VIRTUAL] Antibody responses of cows immunized with HIV V2-apex focusing immunogens (IAS-HIV 2021) - "BACKGROUND: We have previously reported on the elicitation of broadly neutralizing serum antibody responses in cows following homologous prime and boosting immunization with the BG505 SOSIP.664 gp140 trimer... Compared to the previous cow experiment, neutralization breadth was not elicited with a single trimer immunogen, only a subset of cows developed broad responses, and robust responses were only observed later in the immunization sequence. These results indicate that availability of a high frequency of long HCDR3s was insufficient alone to elicit a robust V2apex bnAbs but that a prime-boost strategy could be successful."

Human Immunodeficiency Virus • Immunology • Infectious Disease

[VIRTUAL] Monoclonal antibodies with ultra-long CDRH3 derived from vaccinated cows show exceptional neutralisation potency and breadth that is retained after Fc engineering (HIVR4P 2021) - "Here we used a stabilized trimer gp140 SOSIPv4.1 from the neutralisation resistant ADA subtype-B strain to select a lineage of chimeric human monoclonal BrNAbs containing bovine V-regions with ultra-long CDRH3. To produce monoclonal BrNAbs (mAbs), bovine memory B-cells were isolated from cows vaccinated with AD8 gp140 (clade B), AD8 SOSIP gp140v4.1 or KNH1 SOSIP gp140 and BG505 SOSIP.664 gp140. BrNAbs with novel structured ultra-long CDRH3 from Env vaccinated cows give new insights into conserved gp120-CD4bs epitopes."

Human Immunodeficiency Virus • Infectious Disease • CD4

[VIRTUAL] Intradermal MVA vaccinations provide superior protection compared to intramuscular MVA vaccinations against a homologous tier 2 SHIV challenge (AIDS 2020) - "Soluble BG505-SOSIP.664 trimer protein plus 3M-052 adjuvant encapsulated in nanoparticles was used as a protein boost... Both groups (ID and IM) showed strong binding antibody response to BG505-SOSIP.664 gp140 in serum/vaginal secretions, and some animals generated autologous neutralizing antibody response against BG505.664 Env but these were comparable between the groups... These results demonstrate that MVA-ID vaccination is superior to MVA-IM vaccination for protection against HIV and the route of MVA vaccination markedly influences the quality of T helper response and innate activation that are associated with difference in protection outcome."

Infectious Disease • CD14 • CD8 • IFNG

Antibody responses elicited by immunization with BG505 trimer-immune complexes. (PubMed, J Virol) - "To overcome this problem, we attempted to mask immunodominant glycan holes by immunizing rabbits with ICs consisting of the BG505 SOSIP.664 gp140 trimer and MAbs that targeted the glycan holes...Our results suggest that selective epitope dampening of BG505 trimers by ICs is rather ineffective. However, IC vaccination may represent a novel means of increasing the duration of vaccine-induced antibody responses."

Journal • Infectious Disease

Evaluating the Safety and Immunogenicity of HIV-1 BG505 SOSIP.664 gp140 With TLR Agonist and/or Alum Adjuvants in Healthy, HIV-uninfected Adults (clinicaltrials.gov) - P1; N=105; Recruiting; Sponsor: National Institute of Allergy and Infectious Diseases (NIAID); Active, not recruiting ➔ Recruiting

Clinical • Enrollment open

Evaluating the Safety and Immunogenicity of HIV-1 BG505 SOSIP.664 gp140 With TLR Agonist and/or Alum Adjuvants in Healthy, HIV-uninfected Adults (clinicaltrials.gov) - P1; N=105; Active, not recruiting; Sponsor: National Institute of Allergy and Infectious Diseases (NIAID); Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed

Evaluating the Safety and Immunogenicity of HIV-1 BG505 SOSIP.664 gp140 With TLR Agonist and/or Alum Adjuvants in Healthy, HIV-uninfected Adults (clinicaltrials.gov) - P1; N=105; Recruiting; Sponsor: National Institute of Allergy and Infectious Diseases (NIAID); Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • PCR

Evaluating the Safety and Immunogenicity of HIV-1 BG505 SOSIP.664 gp140 With TLR Agonist and/or Alum Adjuvants in Healthy, HIV-uninfected Adults (clinicaltrials.gov) - P1; N=105; Not yet recruiting; Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Clinical • New P1 trial