Nonlive vaccines are typically given in a single dose, in contrast to a natural infection, which exposes the immune system to escalating antigen levels over time. Researchers investigated the efficacy of administering escalating doses of HIV antigen to mice over a 1–2 week time period, via repeated injection or osmotic pumps, compared with single-dose vaccination.

Exponentially increasing antigen dose over 2 weeks increased antibody concentration more than 10-fold, relative to single-dose immunization. Exponentially increasing antigen dose over time also led to increased antibody concentration, relative to maintaining or decreasing antigen dose over time.

Computational modeling suggested that exponentially increasing the dose leads to prolonged antigen retention in lymph nodes and allows time for higher-affinity antibodies to develop. Prompted by this model, the authors injected mice with the fluorescent protein phycoerythrin.

Little or no antigen could be detected in lymph nodes 24 hours after single-dose immunization, while substantial amounts of antigen could be detected in lymph nodes 24 hours after the final injection in the exponentially increasing regimen.

Taken together, the results suggest that regulating antigen kinetics may lead to effective vaccines against pathogens such as HIV, according to the authors.

http://www.pnas.org/content/early/2016/10/03/1606050113