Rational design of a cross-type HPV vaccine through immunodominance shift guided by a cross-neutralizing antibody.

In vaccine development, broadly or cross-type neutralizing antibodies (bnAbs or cnAbs) are frequently targeted to enhance protection. Utilizing immunodominant antibodies could help fine-tune vaccine immunogenicity and augment the precision of immunization strategies. However, the methodologies to capitalize on the attributes of bnAbs in vaccine design have not been clearly elucidated. In this study, we discovered a cross-type neutralizing monoclonal antibody, 13H5, against human papillomavirus 6 (HPV6) and HPV11. This nAb exhibited a marked preference for HPV6, demonstrating superior binding activity to virus-like particles (VLPs) and significantly higher prevalence in anti-HPV6 human serum as compared to HPV11 antiserum (90% vs. 31%). Through co-crystal structural analysis of the HPV6 L1 pentamer:13H5 complex, we delineated the epitope as spanning four segments of amino acids (Phe42-Ala47, Gly172-Asp173, Glu255-Val275, and Val337-Tyr351) on the L1 surface loops. Further interaction analysis and site-directed mutagenesis revealed that the Ser341 residue in the HPV6 HI loop plays a critical role in the interaction between 13H5 and L1. Substituting Ser341 with alanine, which is the residue type present in HPV11 L1, almost completely abolished binding activity to 13H5. By swapping amino acids in the HPV11 HI loop with corresponding residues in HPV6 L1 (Ser341, Thr338, and Thr339), we engineered chimeric HPV11-6HI VLPs. Remarkably, the chimeric HPV11-6HI VLPs shifted the high immunodominance of 13H5 from HPV6 to the engineered VLPs and yielded comparable neutralization titers for both HPV6 and HPV11 in mice and non-human primates. This approach paves the way for the design of broadly protective vaccines from antibodies within the main immunization reservoir.

[Analysis of factors correlated to death and reinfarction in patients with acute myocardial infarction].

OBJECTIVE: To identify the predictors of death and reinfarction in patients with acute myocardial infarction (AMI) treated with urokinase (UK) thrombolysis or percutaneous transluminal coronary angioplasty (PTCA). METHODS: In ambispective cohort study, 97 cases of AMI were treated with UK thrombolytic therapy, while 93 cases of AMI were treated with PTCA. The patients' data about clinical outcome during hospital and follow-up periods were collected. Death and reinfarction were defined as adverse event. To analyze the correlative factors and independent predictors of death and reinfarction, the spearman rank correlation and multivariate logistic regression modeling were performed. RESULTS: During hospital,incidences of adverse event were 15.46 percent and 6.45 percent in UK and PTCA groups respectively. In follow-up period, they were 30.93 percent and 9.68 percent respectively. Age, Q wave leads, Kill ip class, heart failure in hospital, the history of hypertension and myocardial infarction were positive correlation with adverse event, whereas history of smoking, systolic blood pressure and ejection fraction (EF) showed negative correlation with the adverse event. The interventional therapy, associated with lower mortality and reinfarction rate, was the independent predictor for adverse event in UK and PTCA groups during hospital and follow-up periods. Furthermore, it was the only independent predictor for PTCA group. In UK group, the adverse event also was independently predicted by age, heart failure and Q wave leads in hospital and by age, heart failure during follow-up period. There was negative correlation between preinfarction angina and adverse event, and positive correlation between thrombolysis and adverse event inpatients undergone rescue PTCA. CONCLUSION: Interventional therapy is crucial independent predictor for adverse event of patients suffering from AMI. The adverse event is also predicted by age, Q wave leads and heart failure. The history of preinfarction angina is negative correlation with the adverse event in hospital, due to, maybe, myocardium ischemia preconditioning.