Transient pain and long-term gain: adjuvant dose directs immune memory

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Abstract

Vaccine hesitancy is often fueled by fears of side effects; however, most reactions result from innate immune activation and cytokine production, which are required for lasting immunity. For effective vaccines against HIV, innate activation is essential for differentiation of CD4+ T cells into T follicular helper cells (TFH), which guide rare B cells to mature into long-lived plasma cells that produce durable neutralizing antibodies (nAbs). In this issue of the JCI, Parham Ramezani-Rad et al. show that higher doses of saponin QS-21–MPLA nanoparticle (SMNP) adjuvant, combined with BG505 MD39 envelope (Env) protein, enhanced cytokine responses, drove stronger Env-specific TFH responses in blood, and increased Env-specific bone marrow plasma cells compared with lower doses. While tier 2 nAbs were sustained at memory in only a subset of animals, predominantly at the highest adjuvant dose, these findings highlight transient reactogenicity as an essential mechanism — not a flaw — for building durable immune memory.

Authors

Pabitra B. Pal, Smita S. Iyer