Safety of hepatitis E vaccination for pregnancy: a post-hoc analysis of a randomized, double-blind, controlled phase 3 clinical trial.

Special attention has been paid to Hepatitis E (HE) prophylaxis for pregnant women due to poor prognosis of HE in this population. We conducted a post-hoc analysis based on the randomized, double-blind, HE vaccine (Hecolin)-controlled phase 3 clinical trial of human papillomavirus (HPV) vaccine (Cecolin) conducted in China. Eligible healthy women aged 18-45 years were randomly assigned to receive three doses of Cecolin or Hecolin and were followed up for 66 months. All the pregnancy-related events throughout the study period were closely followed up. The incidences of adverse events, pregnancy complications, and adverse pregnancy outcomes were analysed based on the vaccine group, maternal age, and interval between vaccination and pregnancy onset. During the study period, 1263 Hecolin receivers and 1260 Cecolin receivers reported 1684 and 1660 pregnancies, respectively. The participants in the two vaccine groups showed similar maternal and neonatal safety profiles, regardless of maternal age. Among the 140 women who were inadvertently vaccinated during pregnancy, the incidences of adverse reactions had no statistical difference between the two groups (31.8% vs 35.1%, p = 0.6782). The proximal exposure to HE vaccination was not associated with a significantly higher risk of abnormal foetal loss (OR 0.80, 95% CI 0.38-1.70) or neonatal abnormality (OR 2.46, 95% CI 0.74-8.18) than that to HPV vaccination, as did distal exposure. Significant difference was not noted between pregnancies with proximal and distal exposure to HE vaccination. Conclusively, HE vaccination during or shortly before pregnancy is not associated with increased risks for both the pregnant women and pregnancy outcomes.

Inflammation-related adverse reactions following vaccination potentially indicate a stronger immune response.

Concerns about vaccine safety are an important reason for vaccine hesitancy, however, limited information is available on whether common adverse reactions following vaccination affect the immune response. Data from three clinical trials of recombinant vaccines were used in this post hoc analysis to assess the correlation between inflammation-related solicited adverse reactions (ISARs, including local pain, redness, swelling or induration and systematic fever) and immune responses after vaccination. In the phase III trial of the bivalent HPV-16/18 vaccine (Cecolin®), the geometric mean concentrations (GMCs) for IgG anti-HPV-16 and -18 (P<0.001) were significantly higher in participants with any ISAR following vaccination than in those without an ISAR. Local pain, induration, swelling and systemic fever were significantly correlated with higher GMCs for IgG anti-HPV-16 and/or anti-HPV-18, respectively. Furthermore, the analyses of the immunogenicity bridging study of Cecolin® and the phase III trial of a hepatitis E vaccine yielded similar results. Based on these results, we built a scoring model to quantify the inflammation reactions and found that the high score of ISAR indicates the strong vaccine-induced antibody level. In conclusion, this study suggests inflammation-related adverse reactions following vaccination potentially indicate a stronger immune response.

Sex differences in the incidence and clearance of anal human papillomavirus infection among heterosexual men and women in Liuzhou, China: An observational cohort study.

Anal cancer is primarily caused by human papillomavirus (HPV) infection in both men and women. However, little is known about the sex differences in the natural history of anal HPV infection in a heterosexual population. From May 2014 to March 2016, perianal/anal canal (PA) swab samples were collected semiannually from 2,302 heterosexual men and 2,371 heterosexual women aged 18-55 years old in Liuzhou, China. The specimens were genotyped for HPV DNA by polymerase chain reaction. The incidence rate ratio (IRR) and clearance rate ratio (CRR) were used to analyze the sex differences of incidence and clearance by Poisson regression, respectively. The incidences of PA oncogenic HPV in men and women were 3.4 per 1,000 person-months and 8.6 per 1,000 person-months, respectively, with an IRR of 0.39 (95% confidence interval (CI), 0.29-0.54 for men versus women) (p < 0.0001). The CRR of PA oncogenic HPV infection for men versus women was 1.54 (95% CI, 1.17-2.03) (p = 0.0022). At 12 months, 44% (20/45) of HPV 16/18 infections among women remained positive, whereas no (0/7) infections persisted among men (p = 0.0350). Both the higher incidence and slower clearance of anal carcinogenic HPV infection among women may lead to a higher burden of anal cancer among women than among men in a heterosexual population.