FORMALIN INACTIVATION OF VESICULAR STOMATITIS-VIRUS IMPAIRS T-CELL- BUT NOT T-HELP-INDEPENDENT B-CELL RESPONSES

The effects of formalin on the infectivity and immunogenicity of vesic ular stomatitis virus (VSV) serotype Indiana were investigated. We fou nd that formalin inactivation of VSV prevents infection of Vero cells in a concentration- and time-dependent manner, as shown by fluorometri c cell analysis and inhibition of plaque formation. Inactivated VSV fa iled to induce significant cytotoxic T-lymphocyte responses in vivo or after restimulation in vitro. In contrast, the early immunoglobulin M (IgM) response, which is T help independent in the VSV system, was un altered, suggesting normal antigenicity for and induction of B cells. However, no switch to IgG occurred, demonstrating failure of induction of T help. If cross-reactive T help was provided by previous infectio n with a second serotype of VSV (New Jersey), the IgG response was alm ost completely restored, confirming that the absence of IgG was due to lack of T help. A formalin-treated preparation of glycoprotein of VSV led to a delayed but otherwise normal IgG response, whereas treatment of VSV with UV light or beta-propiolactone reduced IgG titers to the same extent as did formalin. These results suggest that loss of infect ivity and the ensuing lack of amplification of viral antigens of forma ldehyde-inactivated VSV is the major factor impairing induction of spe cific T-helper cell responses.