Recombinant Herpes simplex virus type 1 vectors induce protective immune responses against Listeria monocytogenes but the vaccine efficacy is strongly affected by preexisting host immunity

Henning Lauterbach, LMU Munich, Institute for Immunology

e-mail: henning.lauterbach@ifi.med.uni-muenchen.de

Many microbial organisms and viruses have coevolved with their hosts to overcome protective immune responses. For vaccines targeting specifically intracellular pathogens the induction of cytotoxic and Th1 helper cellular immune responses is highly desirable. Therefore, a new form of vaccination, using genetically engineered virus vectors, is under intensive investigation. As herpes simplex virus type 1 (HSV-1) based vectors offer many advantages, like a broad host range, the ability to transduce dividing and nondividing cells and a large transgene capacity, we developed a replication deficient, recombinant HSV-1 (rHSV-1) vaccine. We demonstrate that, in direct comparison to DNA vaccination, rHSV-1 induces extremely potent antigen specific CTLs, whereas the DNA vaccine induces much stronger CD4 T cell help and humoral responses. Furthermore, we examined the efficacy of these two vaccines in providing protection against infection with Listeria monocytogenes. While both vaccines were capable of confering protection against infection with a moderate, but lethal L. monocytogenes dose, only immunization with rHSV-1 could protect mice from a high dose. However, in the light of the high prevalence of HSV in the human population, one concern that affects all virus based vaccines is the impairment by preexisting host immunity, diminishing the efficacy of the vaccine. Therefore, we investigated the consequence of preexisting immunity on the vaccine response induced by our recombinant HSV-1 vector.