HIV broadly neutralizing antibody precursors to the Apex epitope induced in nonhuman primates

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Conflicts of Interest

Identified Weaknesses

Rating Explanation

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Paper Summary

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Monkeying Around with HIV: Promising Vaccine Steps Using ApexGT6

This study, conducted in rhesus macaques, showed that two versions of an HIV vaccine candidate (ApexGT6, delivered as a protein or mRNA) successfully primed the immune system to create antibody precursors targeting the Apex region of the HIV envelope protein. Further research is needed to determine if these precursor responses can be guided to develop into mature broadly neutralizing antibodies in humans. Notably, the mRNA version induced precursors with longer HCDR3s, potentially advantageous for future vaccine development.

Possible Conflicts of Interest

Some authors are employed by and/or have filed patents related to Moderna, Inc. Dr. Burton is a paid consultant of IAVI.

Identified Weaknesses

Animal model

Although the study demonstrates promising results in rhesus macaques, it's important to acknowledge that non-human primate models don't perfectly replicate the human immune system. Therefore, it's uncertain whether these findings will translate directly to humans and further research is needed.

Focus on priming, not full maturation

The study primarily focuses on priming the immune system, the initial step in inducing a long-term antibody response. It doesn't fully explore the subsequent stages of maturation required to generate broadly neutralizing antibodies, which is essential for an effective vaccine.

Low sample size in some analyses

The low number of B cell sequences recovered from some peripheral blood samples limits the assessment of precursor development, particularly for memory B cells in the mRNA immunized group.

Rating Explanation

This study presents strong pre-clinical research in a relevant animal model, demonstrating consistent induction of precursor antibodies targeting a key HIV vulnerability. Although conducted in monkeys and focused on priming, not full antibody maturation, the findings represent a significant advance in HIV vaccine development, warranting a rating of 4. The association with Moderna and IAVI raises a potential conflict of interest, but doesn't invalidate the research itself.

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