Therapeutic vaccination against HSV-2: influence of vaccine formulation onimmune responses and protection in mice

Therapeutic immunisation may represent a means of influencing viral infecti ons that persist in the host by modulating the nature or level of host immu nity. To assess the influence of the form of the antigenic stimulus on immu nity to type-2 herpes simplex virus (HSV-2), mice pre-infected with subleth al doses of HSV-2 were immunised with various HSV-2 vaccine formulations pr ior to challenge infection with heterologous HSV-1. Measurements of interle ukin-2 (IL-2), interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) levels in mouse spleen cell cultures restimulated in vitro with HSV-2. antigens s howed that, depending on the form of HSV-2 antigen preparation used in this therapeutic context, changes in the levels of these cytokines could be eff ected. Measurement of HSV-specific antibody by serological tests support th e contention that immunisation of HSV-2-infected mice can either enhance th e existing Th1-like immune response elicited following HSV-2 infection, or modulate this response towards a more Th2-like profile, and this is depende nt on the form of the antigenic stimulus. The degree of protection against subsequent lethal, heterologous HSV-1 challenge infection varied according to the nature of the infection and the immunisation history of the animals. (C) 2000 Elsevier Science Ltd. All rights reserved.