ABSTRACT
Objective To analyze the mucosal immune responses induced in BALB/c mice after immunization with Vaccinia Tiantan-based HIV vaccine in combination with protein and to evaluate the effi-cacy of different immune strategies and adjuvants.Methods The BALB/c mice were intramuscularly or in-tranasally immunized with the recombinant Vaccinia virus Tiantan strain ( rTV) carrying CN54 Gag-Pol-Env gene and boosted with the gp140 protein and MF59 adjuvant by intramuscular, intranasal or subcutaneous in-jection.Serum, saliva and vaginal lavage samples were collected from the BALB/c mice.The titers of anti-gen specific IgG and IgA were detected by ELISA.Results Significantly enhanced mucosal immune respon-ses were induced by immunization with gp140 protein used in combination with MF59 adjuvant.The IgA an-tibodies elicited in mice mucosal tissues by gp140 protein and MF59 adjuvant were as high as those induced by gp140 protein and cholera toxin subunit B or recombinant flagellin adjuvant.High tiers of gp140-specific IgA antibodies were observed in serum, saliva and vaginal lavage samples from the mice intramuscularly primed with rTV and intranasally boosted with gp140 protein and MF59 adjuvant.The tiers of IgA antibodies in serum and mucosal tissue samples were 1 ∶15 000 and 1 ∶600, respectively.Conclusion High titers of mucosal IgA antibodies were elicited in BALB/c mice intramuscularly primed with Vaccinia Tiantan-based HIV vaccine and intranasally boosted with gp140 protein and MF59 adjuvant, especially in vaginal and oral tissues.This immunization strategy might be able to block the heterosexual transmission of HIV-1 through va-ginal and oral mucosa.
ABSTRACT
Objective To describe the natural history of cervical intraepithelial neoplasia(CIN)Ⅰand the biologic factors associated with the progression of CINⅠ and to analyze the predictive values of p16INK4a protein for the progression of CINⅠ. Methods From August 2010 to July 2013, 104 patients referred for abnormal cytology [≤ low-grade squamous intraepithelial lesion (LSIL); including negative for intraepithelial lesion or malignancy (NILM), atypical squamous cells of undetermined significance (ASCUS), LSIL] and high-risk (HR) HPV positive,and were diagnosed CINⅠ by colposcopy-assisted biopsy and followed at 1-year intervals in the First Affiliated Hospital of Nanjing Medical University. In order to analyze the relationship between the progression of CINⅠ with clinical biologic factors, including patient age, cervical cytology before colposcopy, loads of HR HPV, HPV L1 capsid protein, p16INK4a protein,χ2 tests was used to compare the different frequencies of factors in groups of progressed and persisted/regressed CINⅠ, then five factors with progressed CINⅠwere processed into binary logistic regression analysis. Results (1) In the first year of follow-up, among 104 patients(including 15 cases NILM,78 cases ASCUS,11 cases LSIL), 52 cases of them were NILM and HR HPV negative, 30 cases were negative for intraepithelial lesion, 10 cases were CINⅠ, 5 cases were CINⅡand 7 cases were CINⅢ. In total, 82 cases (78.8%,82/104) cases had regressed, 10 cases (9.6%,10/104) persisted, 12 cases (11.5%,12/104) progressed [including 5 cases (4.8%,5/104) progressed to CIN Ⅱ, 7 cases (6.7%,7/104) progressed to CIN Ⅲ, none progressed to invasive cancer]. (2) All patients, 88 cases of them accepted immunohistochemical detection the expression of p16INK4a protein. The result shown that 30 cases (34%,30/88) were positive and 58 cases (66%,58/88) were negative. And 94 cases accepted immunocytochemical detection the expression of HPV L1 capsid protein, 49 cases (52%,49/94) were positive and 45 cases (48%,45/94) were negative. (3) Univariate analysis showed that age of the patient, loads of HR HPV, cervical cytology before colposcopy and the expression of HPV L1 capsid protein were not risk factors of the progression of CINⅠ(all P>0.05) except for the expression of p16INK4a protein (P<0.05). Multivariable analysis found that p16INK4a protein positive was associated with progression of CINⅠ(OR=5.1,95%CI:1.162-22.387,P=0.031). (4) Thirty-one cases were p16INK4a protein positive, 8 cases (27%,8/30) of them progressed,while 4 cases (7%,4/58) of 58 cases with p16INK4a protein negative progressed,in which there were significant difference (P<0.05). The sensitivity was 75%, the specificity was 71%, the positive predictive value was 27%and the negative predictive value was 93%for progression to CINⅡ-Ⅲof p16INK4a protein staining. Conclusions The progression rate of CINⅠwith abnormal cytology (≤LSIL) and HR HPV positive was lower, and there was no progression to invasion at 1-year intervals. Immunostaining of p16INK4a protein as the risk factors of CINⅠprogression could have a role in prediction of CINⅠand the management of high-risk CINⅠ.