A vaccine for HIV has been elusive. Traditional approaches to vaccine development have been largely unsuccessful in clinical trials with modest efficacy observed only for a canarypox prime/gp120 boost combination (RV144 trial). Evidence is now emerging from preclinical trials that early control of HIV replication at the site of infection can prevent systemic loss of CD4 T cells. An opportunity to do this is also presented by the characterisation of a new class of memory T cells, called ‘Tissue Resident memory T cells’ (TRM), which reside in epithelial tissues. We present a strategy to generate HIV-specific TRM at sites of HIV infection by coupling vaccination with a mild inflammatory signal to ‘pull’ circulating HIV-specific CD8 T cells into the mucosa, where they will differentiate into sessile TRM in the epithelium. Their inherent capacity to respond rapidly to the initial focus of infection can, in theory, prevent the dissemination of virus.
We have prepared and evaluated Influenza virus as a vaccine vector in mice. The HIV p24 capsid gene was cloned into the non-structural segment. Expression of p24 was observed in lung epithelial cells and vaccination of mice using a prime/boost vaccination regimen with heterosubtypic influenza induced a robust immune response. We are now poised to test the pull strategy and evaluate protection.