Hepatitis E virus (HEV) is a significant public health concern worldwide. Pregnant women are at high risk of severe HEV infection. Various adverse outcomes in pregnant women related to HEV infection have been well documented in low-income and middle-income countries with poor sanitation. However, previous studies have provided inconsistent conclusions regarding the effects of HEV infection on the health of pregnant women and their infants in developed countries and contemporary China. In China, previous studies on HEV in pregnant women mainly focused on anti-HEV IgM and/or anti-HEV IgG. In this study, 4244 pregnant women were retrospectively analyzed for HEV-related markers. The positive rates of HEV antigen, HEV RNA, anti-HEV IgM, and anti-HEV IgG were 0.28%, 0.54%, 0.35%, and 10.49%, respectively. Among the 467 pregnant women who tested positive for at least one HEV-related marker, 92.93% (434) were positive for anti-HEV IgG only and 0.21% (1) were positive for HEV antigen, anti-HEV IgM, and anti-HEV IgG. Although the prevalence of anti-HEV IgG significantly increased with age, the prevalence of anti-HEV IgM, HEV RNA, and HEV antigen did not differ among pregnant women of different ages. Thirty-three pregnant women were positive for at least one of anti-HEV IgM, HEV antigen, and HEV RNA, and these individuals were recently or currently infected with HEV. None of the 33 pregnant women exhibited obvious clinical symptoms. Of the 33 pregnant women, 39.39% (13) experienced adverse fetal outcomes, including preterm birth, fetal distress, and low birth weight, the incidence of which was significantly higher than in pregnant women who were not recently or currently infected with HEV. These findings suggest that maternal HEV infection may impact the health of fetuses; thus, these results may contribute to the development of appropriate public health interventions for this population.

Paslahepevirus balayani (bHEV), also known as hepatitis E virus (HEV), encompasses eight genotypes, five of which infect humans. Rats are natural reservoirs of Rocahepevirus ratti genotype 1 (HEV-r-1; rat HEV; rHEV), which has recently been implicated in viral hepatitis. Despite the antigenic divergence between bHEV and rHEV, studies on shared protective antibodies remain rare. Polyclonal and monoclonal antibody responses against bHEV and rHEV were analyzed using antibody enzyme-linked immunosorbent assays. The efficacy of six potent bHEV-elicited cross-reactive antibodies in preventing rHEV infection was evaluated via challenge assays in rats. Cryo-EM was performed to assess the structural basis for the differential protective efficacy of the six antibodies. The viral lysis ability of these antibodies was assessed by separately reacting purified HEV-b-1 and HEV-r-1 virions with each antibody. We determined that antibody responses to bHEV infection and vaccination possess limited cross-reactivity to rHEV and identified two cross-reactive antigenic sites within the E2s domain. Structural analysis and animal challenge studies pinpointed potent cross-reactive antibodies targeting antigenic site 1, indicating its prophylactic efficacy against rHEV. Conversely, antibodies recognizing antigenic site 2 were found to facilitate viral lysis of bHEV but not rHEV. These findings underscore the importance of antigenic site 1 in the design of broad-spectrum vaccines and therapeutics to mitigate the impact of diverse HEV genotypes on human health. IMPACT AND IMPLICATIONS: rHEV spillover to humans represents an unprecedented threat. Significant antigenic differences between rHEV and bHEV may exacerbate the impact of viral hepatitis. Our study reveals that cross-reactive human antibodies can offer protection against rHEV infection. Cross-protective antibodies targeting antigenic site 1 can be used to inform the development of practical strategies for preventing rHEV infection.

During pregnancy, profound immunological, hormonal, and metabolic adaptations occur to support fetal development. The impact of pregnancy on vaccine-induced immunity remains incompletely characterized, as previous studies have primarily focused on serological antibody levels but not immune memory. Immune memory is critical for vaccine effectiveness, but effect of pregnancy on immune memory remain unknown. In addition, the memory B cell response profile induced by inactivated coronavirus disease 2019 (COVID-19) vaccines in pregnant women remains unclear. This study comprehensively investigated the serological responses and memory B cell response induced by an inactivated COVID-19 vaccine in pregnant women. The results demonstrated that while pregnant women and non-pregnant women of childbearing age showed comparable serological antibody levels, vaccine-induced monoclonal antibodies (mAbs) from pregnant women exhibited significantly lower binding potency to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein and its segments and weaker neutralizing potency and breadth than those from non-pregnant women. Vaccine-induced mAbs from pregnant women were derived predominantly from IGHV3-30, whereas those from non-pregnant women were derived diverse germline genes. Most of mAbs from pregnant women targeted the receptor-binding domain (RBD) (40.9%) and S2 domain (31.8%), whereas most of mAbs from non-pregnant women targeted the RBD (51.3%) and N-terminal domain (30.8%). These findings suggested that pregnancy may impair the potency of vaccine-induced memory B cells. These insights may be valuable for the development of vaccination strategies for pregnant women.

Hepatitis E virus (HEV) is a significant pathogen causing acute viral hepatitis globally, posing a particular threat to pregnant women. HEV infects a range of host species, with distinct genotypes exhibiting genotype-specific tropism for different host hepatocytes. The P domain of viral capsid protein plays a central role in host cell attachment, but the molecular determinants that govern its host specificity remain unclear. This study investigates the molecular mechanisms underlying HEV host tropism by using a zoonotic HEV specific antibody 6H8. An epitope involving residues 490 and 492 is identified crucial for both mAb 6H8 binding and virus-cell attachment. Structure-based mutagenesis, molecular dynamics simulations, virus-cell attachment assays, and viral infectivity assays highlight the importance of the N490 and M492 residues in maintaining the structural integrity of the 6H8 epitope, influencing host specificity. Mutations at 490 and 492 permit HEV-1’s and disrupt HEV-4’s binding and infection in porcine hepatocytes. However, they are insufficient alone for reestablishing swine infection in vivo, indicating additional factors are involved in HEV’s host tropism. Our findings suggest that N490 and M492 are critical but not sole determinants of HEV-4’s specific tropism for porcine hepatocytes and advance our understanding of HEV’s zoonotic transmission and host specificity.

Hepatitis E virus (HEV) is a major global public health concern, particularly in resource-limited regions. Approximately 12.5% of individuals worldwide have been exposed to HEV, and 15–110 million individuals have current or recent HEV infection. HEV poses an especially serious threat to pregnant women, in whom infection can progress to severe disease and is associated with a high case fatality rate, particularly during the third trimester. Moreover, maternal HEV infection can lead to various adverse outcomes in fetuses and/or neonates, as documented in both developing and developed countries. No HEV-specific antiviral therapy is approved for use during pregnancy, and pregnancy-specific evidence and recommendations for HEV vaccination remain limited. This narrative review summarizes the diagnosis, prevalence, clinical manifestations, mechanisms underlying severe disease, treatment, and prevention of HEV infection in this high-risk population. It aims to improve clinicians’ awareness of the potential impact of HEV infection on pregnant women and their fetuses/neonates, to promote public health literacy, and to accelerate future disease-control efforts.