四价与九价人乳头瘤病毒疫苗在已接种二价疫苗女性中的序贯接种免疫应答研究

Objective To investigate the immune response to sequential vaccination with quadrivalent and nonavalent human papillomavirus(HPV) vaccines in women who had previously received a bivalent vaccine. Methods A total of 360 women who had received a bivalent vaccine between January 2024 and December 2025 were enrolled and divided into a quadrivalent sequential group(n=180) and a nonavalent sequential group(n=180) based on random number table method. Each group received either a single dose of the quadrivalent or nonavalent HPV vaccine. Serum samples were collected one month post-vaccination, and antibody positivity rates and titers were compared. The correlation between age and antibody titer levels for each serotype was also analyzed. Results One month after sequential vaccination, there was no statistically significant difference in antibody positivity rates for HPV types 6, 11,16, and 18 between the two groups(P>0.05). The nonavalent sequential group exhibited higher antibody positivity rates against the five newly added highrisk types(HPV 31,33,45,52, and 58) compared to the quadrivalent sequential group(P<0.05). Neutralizing antibody titers demonstrated that for the four common HPV types(6, 11,16, and 18), both groups achieved high antibody titers, with no statistically significant differences between them(P>0.05). The nonavalent sequential group successfully induced high levels of neutralizing antibodies against the newly added types HPV 31,33,45,52, and 58, with higher antibody titers than the quadrivalent sequential group(P<0.05). In the quadrivalent sequential group, age showed a negative correlation with HPV type 11 antibody titers, whereas in the nonavalent sequential group, age exhibited negative correlations with antibody titers against HPV types 31,45, and 52(P<0.05). Conclusion Sequential administration of the nonavalent HPV vaccine effectively induces immune responses against five additional high-risk genotypes, with immune-boosting efficacy against the original genotypes comparable to that of sequential quadrivalent vaccination. Furthermore, advancing age may exhibit a negative correlation with antibody titer strength against certain newly identified genotypes. For individuals who have completed bivalent vaccination, sequential administration of the nonavalent vaccine demonstrates favorable efficacy in broadening protective coverage.