Table 2 Translating insights from studies of infection into novel immunization strategies
From: Development of broadly neutralizing antibodies in HIV-1 infected elite neutralizers
Mechanism in infection | Immunization | ||
|---|---|---|---|
1 | High viral load | Recruitment of larger B and T cell repertoires by increasing chances of activating lower affinity precursors due to higher antigen concentration | Germline-targeting immunogen design based on UCA features → high affinity prime Adjuvants to boost innate immune responses |
2a | High anti-Env IgG Titers and helper lineages of neutralizing antibodies | More diverse repertoire increases chance of productive bNAb UCA encountering antigen May restrict/slow down viral escape | Adjuvants to ensure high Ab titers and posibly greater diversity Sustained delivery to ensure prolonged availability of Ags Adjuvants to boost innate immune responses |
2b | High frequency of Tfh | May increase chances of activating lower affinity intermediates with unusual features, thereby sustaining affinity maturation and leading to higher SHM levels | Formulation should include T-cell epitopes Adjuvants to boost innate immune responses and GC reaction |
3 | Burst of viral diversity | Increased chances of activating/maturing low affinity intermediates with unusual features. Sustained affinity maturation and associated high levels of SHM | Immunogen design incorporating incremental diversity. Autologous versus heterologous boosts to avoid “dead-end” pathways Contemporaneous delivery of “variants” to quickly select relevant intermediates and positive selection |