Kirby Institute Seminar Series presents
Senior Investigator, Animal Models and Vaccine Section, Center for Cancer Research, National Cancer Institute, USA
About your speaker
Dr Genoveffa Franchini is a hematologist and retrovirologist who has pioneered research on oncogenes and human retroviruses (HTLVs and HIVs). Her work has furthered the understanding of HTLV-1 pathogenesis and gene regulations, and has led to the first partially efficacious HIV vaccine in humans.
We contrasted innate and adaptive immune responses of HIV vaccine candidates of varying efficacy in macaques that shared the ALVAC + gp120 protein boost with an ALVAC, DNA or Ad26 prime modality. Comparison of the immunogenicity of the DNA and ALVAC prime regimens, both protective, to that of the non-protective Ad26 prime revealed that vaccine efficacy was associated with qualitative temporal-spatial differences in the innate CD14+ and CD16+ cells in blood and tissues. The activation of hypoxia and the inflammasome in CD14+DR+ CD16- classical monocytes and CD4+ Th2 responses correlated with a decreased risk of SIVmac251 acquisition. CD4+ Th2 cells, in turn, correlated with mucosal NKp44+ cells and mucosal protective antibodies to V2. In contrast, the Ad26 prime resulted in increased de novo differentiated CX3CR1+CD163+ macrophages in lymph nodes, increased CD4+ Th17 cells in blood and rectal mucosa, and an overall lack of vaccine efficacy. These data posit that the engagement of classical monocytes and inflammasome activation is central for the elicitation of protective innate and adaptive responses by the ALVAC-based HIV vaccine platform.
A catered lunch will be provided at 12:30pm. Please RSVP to firstname.lastname@example.org by COB Monday 6 November.