A major challenge for immunologists has been the development of vaccines able to augment both of humoral and cellular immune responses. One particularly promising approach is the prime–boost strategy, which has been shown to generate high levels of T-cell memory in animal models. In the present study, HIV-1 gp41 (662-683) loaded liposomes were used to determine how does prime–boost strategy would be beneficial for generation of humoral and cellular responses. BALB/c mice were immunized with HIV-1 gp41 (662-683) liposomes and 30 days later they received the booster doseof the same immunogen. HIV-1 gp41 (662-683) specific humoralresponse was evaluated pre-prime, 30days post-prime and 30 days post-boost by ELISA. HIV-1 gp41 (662-683) specific antibodies sharply jumped after boosting by ~40 foldcompared to that generated by priming. Similarly, self-boosting generated considerably HIV-1 gp41 (662-683) specific antigen secreting plasma cells in bone marrow. Overall, the results suggest that self-boosting is very important for generation of specific humoral response for HIV-1 gp41 (662-683). This prime-boost strategy shows a promise to induce both of specific-antibodies and specific antibody secreting cells in bone marrowfor weak immunogens like HIV-1 gp41 (662-683).