Pre-existing immunity against Ad vectors: Humoral, cellular, and innate response, what's important?

Fausther-Bovendo, Hugues; Kobinger, Gary P

In addition, heterologous prime-boost regimens involving Ad vectors should be further optimized. The immune response generated by prime-boost regimens may be sufficient to induce full protection despite pre-existing Ad immunity. Developing prime-boost regimens using Ad vectors where limited to no nAbs or cross-reactive T cells in the target population should further increase the chance of success. However, optimization of prime-boost regimens will be labor intensive due to the increasing number of available vaccine platforms. Useful data regarding the ability of prime-boost regimens to overcome pre-existing HAd immunity will certainly be generated by clinical trials involving ChAd/MVA prime-boost. Careful analysis of these trials should provide crucial protection information in the presence or absence of pre-existing Ad immunity. In addition, future clinical trials involving Ad vectors should also determine whether Ad-based vaccine regimens impact HIV acquisition. Although HAd5 immunization increased HIV acquisition in participants with pre-existing HAd5 immunity in the STEP trial, whether this trend holds true for other Ad vectors expressing different inserts needs to be systematically evaluated. Upcoming clinical trials performed in populations at high risk of HIV infection will address this critical issue.