The HIV pandemic has been a global health emergency for more than 30 years with an annual reoccurrence of 2 million new HIV-infections. Implementation of existing prevention measures has proven challenging, highlighting the need for an efficacious HIV vaccine. However, to date the only HIV vaccine trial to demonstrate even modest efficacy was the RV144 study. The results of this trial identified several key features, such as suggesting correlates of protection, selection of the vaccine-delivery mode, design of the immunogens and optimisation of the immunisation regimen, all are potentially imperative for effective vaccine development.
Optimisation of immunisation schedules is critical for shaping the profile of vaccine- induced immune responses, the primary focus of research in this thesis. The overall aim of the thesis was to evaluate the effect of alternately timed booster regimens on both humoral and cellular immune responses to the candidate HIV-1 Env protein CN54gp140, adjuvanted with GLA-AF. For this purpose, study participants received a common 3-dose intramuscular priming series followed by a final booster at either 6 or 12 months.
The longitudinal tracking of immune responses revealed that the two homologous prime- boost regimens safely and effectively induced CN54gp140-specific responses in systemic and mucosal compartments. Levels of vaccine-induced IgG-subclass antibodies correlated significantly with the engagement of Fc-receptors and both vaccine-regimens were associated with identical patterns in titre and functional antibody response profiles. Additional depth was added to the characterisation of CN54gp140 vaccine regimens through the evaluation of Env- specific monoclonal antibody responses.
In summary, the combined data revealed significant similarities in response magnitude and antibody profiles associated with both immunisation schedules. The findings strongly suggest that the 6-month regimen can be adopted for the rapid induction of immune responses against CN54gp140 without affecting response magnitude, antibody diversity or functionality adversely.