It is difficult to induce protective immunity against most RNA viruses. However, there is strong evidence that humoral and especially cellular immune responses play crucial roles in the control of established RNA viral infections. Herein, correlates of protective immunity against HIV-1, HCV and SARS- CoV were assessed by various strategies. In the first study, we showed that a combination of monocistronic DNA constructs expressing HIV-1 structural genes, HIV-1 recombinant proteins and a potent adjuvant is able to induce humoral and cellular immune responses in HLA.A2.1 mice. In the second HIV-1 study, a synergistic effect between HIV- 1 and hepatitis C (HCV) immunogens was detected that may lead to induction of multi-specific immune responses against both HIV and HCV. In the third study, a high level of specific SARS-CD8+T-cell response was demonstrated in mice that received DNA vaccine expressing the SARS-nucleocapsid, protein and XIAP (X-link inhibitor of apoptosis) as an adjuvant.