2回投与スケジュールでHIVワクチンがより効果的になる可能性(A two-dose schedule could make HIV vaccines more effective)

2024-09-20 マサチューセッツ工科大学(MIT)

<関連情報>

• https://news.mit.edu/2024/two-dose-schedule-could-make-hiv-vaccines-more-effective-0920
• https://www.science.org/doi/10.1126/sciimmunol.adl3755

2回投与によるプライミング免疫により、胚中心反応とワクチン接種を同期させることで体液性免疫が増幅される Two-dose priming immunization amplifies humoral immunity by synchronizing vaccine delivery with the germinal center response

Sachin H. Bhagchandani, Leerang Yang, Jonathan H. Lam, Laura Maiorino, […], and Darrell J. Irvine
Science Immunology  Published:20 Sep 2024
DOI:https://doi.org/10.1126/sciimmunol.adl3755

Editor’s summary

A key feature of effective vaccines is that the delivery strategy optimizes immune responses. Bhagchandani et al. sought to optimize immune responses using prolonged exposure to a protein subunit vaccine called escalating-dose immunization (EDI). They immunized mice with an adjuvanted HIV envelope protein subunit and tested different numbers of doses, dose ratios, and time intervals between doses. A two-dose regimen for which 20% of the vaccine was administered in the first dose and 80% was given in the second dose 7 days later induced effective follicular helper T cell and antigen-specific germinal center B cell responses that were also reflected in higher antibody titers. This response was linked to enhanced antigen capture and presentation by dendritic cells. —Christiana Fogg

Abstract

Prolonging exposure to subunit vaccines during the primary immune response enhances humoral immunity. Escalating-dose immunization (EDI), administering vaccines every other day in an increasing pattern over 2 weeks, is particularly effective but challenging to implement clinically. Here, using an HIV Env trimer/saponin adjuvant vaccine, we explored simplified EDI regimens and found that a two-shot regimen administering 20% of the vaccine followed by the remaining 80% of the dose 7 days later increased T_FH responses 6-fold, antigen-specific germinal center (GC) B cells 10-fold, and serum antibody titers 10-fold compared with bolus immunization. Computational modeling of T_FH priming and the GC response suggested that enhanced activation/antigen loading on dendritic cells and increased capture of antigen delivered in the second dose by follicular dendritic cells contribute to these effects, predictions we verified experimentally. These results suggest that a two-shot priming approach can be used to substantially enhance responses to subunit vaccines.