Targeting enhanced neutralizing antibody responses via increased germinal center activity: early-phase vaccine trials with novel clinical designs

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PURPOSE OF REVIEW: Recent advances in the understanding of the difficult immunologic requirements for the induction of broadly neutralizing antibodies for HIV have spurred interest in optimizing vaccine approaches intended to stimulate a robust germinal center reaction. In preclinical models, techniques to optimize the germinal center response have included alterations in the timing, dose, and delivery method of immunogens and have resulted in substantially enhanced germinal center responses in lymph nodes and neutralizing antibodies in serum. One of the most promising approaches involves splitting the initial dose of vaccine into a series of gradual escalating doses administration ("fractional escalating doses"). In principle, these techniques may have broad implications for vaccines targeting a robust antibody response. RECENT FINDINGS: We review the upcoming vaccine trials that will test these concepts in clinical practice. The trials include both HIV and non-HIV immunogens, and will involve testing these concepts in both healthy adults and immunocompromised persons. SUMMARY: There are multiple trials that will test whether techniques to alter vaccine delivery such as fractional escalating doses enhances immunologic outcomes.

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