Respiratory syncytial virus (RSV) poses a critical threat to infants, yet vaccine and antibody development remains challenged by safety risks and antigenic variability. Here, we present a prophylactic strategy leveraging two human neutralizing antibodies, 1A2 and 1B6, which target distinct, conserved epitopes on the RSV prefusion F (pre-F) protein. Cryo–electron microscopy (cryo-EM) structural analysis revealed that 1A2 binds a “waist” epitope spanning antigenic sites IV/V, whereas 1B6 engages a “head” epitope bridging sites Ø/II/V, collectively stabilizing the pre-F trimer to block conformational transitions critical for viral entry. In vitro escape mutagenesis demonstrated that the 1A2/1B6 cocktail can resist viral escape (>20 passages), contrasting with rapid resistance to nirsevimab (targeting site Ø) and single antibodies [1A2: Gly ⁴⁴⁶ →Glu (G446E); 1B6: Gln ⁹⁴ →Arg (Q94R) or Gln ⁹⁴ →Lys (Q94K)]. Fc engineering extended serum half-lives while ablating effector functions, addressing potential safety concerns. Last, prophylactic administration in rodent models conferred robust protection against RSV A and B strains, including nirsevimab-resistant variants, with a 296-fold reduction in lung viral titers. This dual-epitope approach overcomes limitations of current monotherapies by combining high conservation, synergistic potency, and escape resilience, positioning it as a valuable immunoprophylactic candidate for pediatric RSV prevention.

Severeacute respiratory syndrome coronavirus 2 (SARS-CoV-2) bivalent vaccines show potential against variants but lack a full understanding of the immunological mechanisms that drive broadly neutralizing antibodies (bnAbs). This study explored the immunogenicity of a bivalent vaccine in rhesus macaques, containing spike (S) proteins from the prototype (S _prototype ) and chimeric S protein (S _1628x ). The vaccine induced bnAbs against multiple variants, including challenging subvariants like EG.1, BA.2.86, and JN.1. The monomeric S protein exposed less accessible regions within the receptor-binding domain (RBD) “inner face” and “NTD face” and subdomains 1, eliciting a diverse array of bnAbs against various Omicron subvariants. Notably, antibodies targeting the conserved RBD inner face, such as 4A5, showed potent neutralization across all tested variants. Structural analyses provide insights into the broad protectiveness of these vaccine-elicited nAbs. This study underscores the potential of bivalent vaccines with monomeric spike proteins to confer broad-spectrum immunity, offering a promising direction for future SARS-CoV-2 universal vaccine design.

Nepal is an endemic area for hepatitis E virus (HEV) epidemics. The research on viral hepatitis in Nepal is limited. Serum samples from 170 patients presenting with symptoms of hepatitis were collected from April to May 2014 in Biratnagar, Nepal, and then transported to Xiamen, China, for further evaluation. All samples were tested for HEV RNA, HEV antigen, anti-HEV IgM, anti-HEV IgG and anti-HBc IgM, anti-HCV IgG, and anti-HAV IgM. Sixteen patients were identified as acute hepatitis E with the presence of ≥ 2 HEV acute phase markers (antigen, RNA, and anti-HEV IgM). HEV infection was the major cause of potential active viral hepatitis (59.2%, 16 of 27), followed by HBV (25.9%, 7 of 27, anti-HBc IgM positive), HAV (18.5%, 5 of 27, anti-HAV IgM positive), and HCV (3.7%, 1 of 27, anti-HCV antibodies). All 16 confirmed HE cases were positive for HEV antigen, while 5 cases were HEV RNA positive, as well as 15 anti-HEV IgM positive. The low positive rate of RNA might be related to the collection and/or the transportation of these samples. This study showed that HEV is a major cause of acute hepatitis in developing countries and regions. Application of immunoassay diagnostic kits, especially the HEV antigen tests, showed great potential for HE detection in these countries and regions.