Ectromelia virus (ECTV) is a pox virus similar to smallpox, but whose natural host species is the mouse. This virus is quite virulent, and infection with 103 virus particles will kill 100% of naive mice within 7-10 days post infection. A vaccine strain of ECTV was generated that is avirulent (i.e., does not cause disease in mice), and mice were immunized with this vaccine strain. Approximately 3 months later, mice were challenged with virulent ECTV. One group of vaccinated mice were depleted of CD4 T cells at the time of challenge, and a second group were left intact. Neutralizing antibody titers to the virus were then measured at two weeks and three weeks post challenge. The results of this study showed that mice depleted of CD4 T cells at the time of challenge had significantly lower titers of antibody and significantly higher levels of viral replication than the intact vaccinated mice. A similar impairment of secondary antibody responses to the virus would be seen if, instead of being treated to deplete CD4 T cells, mice were treated with: A An antibody that blocked the type I interferon receptor B An antibody that blocked CD40 ligand on the T cells C A small-molecule inhibitor of the RAG1/2 enzyme D All of the above would have the same effect on the secondary antibody response.