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eOD-GT8 60mer HIV Vaccine

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January 15, 2024
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eOD-GT8 60mer HIV Vaccine Candidate

eOD-GT8 60mer HIV vaccine candidate stimulates rare immune cells with specific properties. Known as broadly neutralizing antibodies (bnAbs), these specialized blood proteins could attach to HIV spikes, proteins on the virion surface that allow the virus to enter human cells, and disable them via important yet difficult-to-access regions that don't vary much from strain to strain. 

Researchers led by Dr. William Schief at the Scripps Research Institute engineered a molecule based on a region of the HIV envelope protein called the CD4 binding site. They developed a modified protein to prime the precursor B cells to react. The protein, eOD-GT8, was designed to incorporate into a self-assembling nanoparticle with 60 copies. The nanoparticle vaccine was previously shown to induce the production of bnAb precursors in mice.

IAVI and Scripps Research are partnering with the biotechnology company Moderna to develop this mRNA-based vaccine candidate (mRNA-1644). Using mRNA technology could significantly accelerate the pace of HIV vaccine development.

A research team led by Drs. Juliana McElrath at the Fred Hutchinson Cancer Center and Adrian McDermott at the U.S National Institutes of Health (NIH) Vaccine Research Center conducted a phase 1 clinical trial of the eOD-GT8 vaccine to begin assessing its safety and efficacy in people. They found that these cells increased in 97% of vaccine recipients after at least one of the two doses. Frequencies of these B cells increased by more than 500-fold compared to before vaccination. The team also examined the receptors that B cells use to recognize pathogens. These receptors resemble antibodies and similarly recognize their targets. Receptors on the eOD-GT8-targeting bnAb-precursor B cells shared several molecular features with bnAbs. The full results were published in Science.org on December 2, 2022.

On May 25, 2023, IAVA reported new research findings from IAVI G001, a first-in-human clinical trial released in Science Translational Medicine. The study found that the protein immunogen used in the study, eOD-GT8 60mer, with adjuvant, elicited a robust immune response in helper T cells in most recipients. 'Our findings demonstrate strong human CD4 T cell responses to an HIV vaccine candidate priming immunogen and identify immunodominant CD4 T cell epitopes that might improve human immune responses to heterologous boost immunogens after this prime vaccination or other human vaccine immunogens.'

eOD-GT8 60mer HIV Vaccine Indication

eOD-GT8 60mer HIV Vaccine candidate is indicated to induce broad and potent antibodies to confer protection against HIV, a fast-mutating virus. 

eOD-GT8 60mer HIV Vaccine Mechanism of Action

VRC01 is a human IgG1 monoclonal antibody that has demonstrated in vitro neutralizing activity against approximately 90% of a diverse panel of HIV strains. It is a next-generation bNAb that targets a conserved region of the CD4 binding site on the HIV envelope gp120. Registry Number: 1412901-55-3 (CAS).

eOD-GT8 60mer HIV Vaccine News

May 25, 2023 - "We showed previously that this vaccine induced the desired B-cell responses from HIV broadly neutralizing antibody precursors. Here, we demonstrated strong CD4 T-cell responses, and we went beyond what is normally done by drilling down to identify the T-cell epitopes and found several broadly immunogenic epitopes that might be useful for developing boosters and other vaccines," said Schief.

December 13, 2022 - The U.S. NIH published an article stating: These findings establish proof of concept and a crucial first step for the strategy of eliciting bnAbs against HIV. But this priming vaccine alone cannot induce the production of mature bnAbs. Booster vaccines will be needed to elicit bnAb production and protection against HIV. The results support further development of such boosters.

December 2, 2022 - The peer-reviewed journal Science published results from a phase 1 study that establish clinical proof of concept for the germline-targeting vaccine design priming strategy, support the development of boosting regimens to generate VRC01-class bnAb responses against HIV, and encourage the application of the germline-targeting strategy to other targets in HIV and other pathogens.

February 3, 2021 - First-in-human clinical trial confirms novel HIV vaccine approach developed by IAVI and Scripps Research. The vaccine successfully stimulated the production of rare immune cells needed to generate antibodies against the fast-mutating virus; the targeted response was detected in 97% of participants who received the vaccine. The study sets the stage for additional clinical trials to refine and extend the approach — with the long-term goal of creating a safe and effective HIV vaccine.

January 11, 2021 - Moderna Provides Business Update and Announces Three New Development Programs in Infectious Disease Vaccines. Today's development programs are mRNA vaccine candidates against seasonal flu, HIV, and the Nipah virus. 

eOD-GT8 60mer HIV Vaccine Clinical Trials

Clinical Trial NCT03547245: A Phase 1 (IAVI G001) Randomized, Double-blind, Placebo-controlled Dosage Escalation Trial to Evaluate the Safety and Immunogenicity of eOD-GT8 60mer Vaccine, Adjuvanted in HIV-uninfected, Healthy Adult Volunteers.

The results of this phase 1 trial can be found here.

Clinical Trial NCT05001373: A Phase 1, (IAVI G002) Randomized, First-in-human, Open-label Study to Evaluate the Safety and Immunogenicity of eOD-GT8 60mer mRNA Vaccine (mRNA-1644) and Core-g28v2 60mer mRNA Vaccine (mRNA-1644v2-Core) in HIV-1 Uninfected Adults in Good General Healt