Differential neutralizing antibody responses to varicella-zoster virus glycoproteins B and E following naked DNA immunization

The only available vaccine against varicella-zoster virus (VZV) consists of the VZV-Oka attenuated but persistent virus strain. Development of a safer , subunit vaccine is therefore desirable. In this prospect, nucleic acid va ccines, expressing truncated forms of VZV glycoproteins B (recgB) and E (re cgE) from which the anchor and the cytoplasmic domains were deleted, were u sed to immunize mice. Vaccination with recgB encoding plasmid elicited a st rong and specific humoral immune response. Total IgG and neutralizing titre s were comparable to those previously obtained by vaccination with purified and adjuvanted native recgB. In contrast, mice immunization with recgE enc oding plasmid only induced a very weak immune response whereas we previousl y showed that vaccination with adjuvanted native or denatured recgE protein led to high neutralizing titres. The weakness of the immune response induc ed by recgE-encoding plasmid depended neither on the deletion of the anchor domain in the gE gene nor on the animal model. Analysis of antibody isotyp es produced by plasmid immunizations revealed a response slightly dominated by IgG2a. Taken together, the data indicate that a VZV subunit vaccine bas ed on adjuvanted recombinant glycoprotein E is more promising than a nuclei c acid-based vaccine strategy. As regards recgB, both vaccination approache s might be appropriate.