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Objective. To test whether intrarnuscular,intranasal, intrarectal and intravaginal administration of HPV 6b L1 virus-like particles (VLPs) could induce immune response in mice and to assess whether intra muscular and mucosal vaccination against HPV is feasible. Methods. HPV6b L1 proteins self-assembled into VLPs in Sf-9 cell in vitro. Mice were immunized on day 0 and 21 with 50 μg HPV 6b L1 VLPs intramuscularly, intranasally, intrarectally and intravagi nally respectively. Sera were collected for testing IgG titer after a further 7 days and 3 months respec tively. Results. After immunizations, all mice developed significant anti-HPV 6b L1 antibody titers in serum by 7 days after the second immunization. The titer of the serum IgG antibody against HPV 6b L1 VLPs in the intramuscularly immunized group was higher than that in the intranasally, intrarectally and intravaginally immunized groups respectively, indicating that both muscular and mucosal administration of HPV 6b L1 VLPs can stimulate a systemic HPV-specific antibody response. Sera of the mice in the in tramuscularly immunized group still maintained a high titer of the serum IgG antibody against HPV 6b L1 VLPs 3 months after the immunization. Conclusion. The results demonstrated that the HPV 6b L1 VLPs maintain strong antigenicity. Immu nization with HPV 6b L1 VLPs via intramuscular and mucosal routes, without adjuvant, can elicit spe cific antibody in sera. These findings suggest that the VLPs are able to induce protective antibodies.