Volume 08 · Issue 04 · 2026

The World Health Organization has updated the Priority Pathogens List based on risk assessments of the world’s endemic pathogens, the majority of which are viruses. This assessment proposed to extend research and preparation to the entire families of Priority Pathogens, rather than just focusing on individual known high-risk pathogens. The 21 viruses on the Priority Pathogens List belong to 13 virus families. Viruses within the same family have similarities in genes, immunogens, immunity, and transmission, etc. A protective immunogen is an antigenic component that can induce a protective immune response in the immune system after the invasion of pathogenic microorganisms, and it always serves as the early focal point of vaccines and treatment method developments during an outbreak. Here, we summarized the protective immunogens of Priority Pathogens, found the common features of protective immunogens of viruses in the same family, and proposed that the development of vaccines and screening of neutralizing antibodies based on this clue may be applied to the prevention and control of the epidemics or even pandemics of these Priority Pathogens.

People living with human immunodeficiency virus (HIV) are highly susceptible to opportunistic fungal infections, such as Talaromyces marneffei, Candida, and Pneumocystis jirovecii, primarily due to their immunocompromised status. These infections often manifest as invasive candidiasis, pneumonia, and other severe diseases. Consequently, diagnostic failures for these specific infections remain a leading cause of HIV-related mortality. This review systematically evaluated the currently available diagnostic tools for these pathogenic fungi. Traditionally, etiologic detection, particularly fungal cultivation, has been considered the gold standard for diagnosis. Simultaneously, methods such as microscopic examination, molecular biology tests, and immunological diagnostic technologies are rapidly advancing and becoming increasingly applicable. However, persistent limitations in efficiency, accuracy, reliability, and cost-effectiveness continue to impede clinical diagnosis. This dilemma significantly hampers the advancement of clinical diagnosis for opportunistic fungal infections in HIV-positive populations both in China and globally. Given this diagnostic challenge, there is an urgent need for the further development of novel tools and strategies. These efforts should focus on promoting the identification of molecular targets, innovating targeted probes, exploring detection platforms, and designing diagnostic techniques. Ultimately, improvements in the clinical diagnosis of opportunistic fungal infections will directly contribute to a reduction in the HIV-related mortality rate.

Imported aerosol exposure systems for nonhuman primates are often costly and limited in availability, restricting advanced research on respiratory pathogens. To address this, a domestically developed nose-only aerosol exposure system was systematically evaluated and optimized to enhance performance and accessibility. Comprehensive assessment of aerosol generation, transmission, and sampling components revealed key areas for improvement, which were targeted through four modifications: adoption of a vibrating mesh nebulizer for physiologically relevant particle sizes, reduction of plenum chamber volume to minimize losses, shortening of transmission pathways, and addition of 0.25% newborn calf serum to sampling media for viral preservation. These changes collectively minimized viral viability loss during aerosol delivery. The optimizations resulted in a 2.19 log10-units increase in spray factor (SF), enabling aerosol concentrations to exceed 104.43 50% cell culture infectious dose (CCID50)/L at the exposure port using 107.25 CCID50/mL viral titer in the generator. Functional evaluation with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in cynomolgus macaques (Macaca fascicularis) provided preliminary evidence of feasibility for viral delivery and infection, with detectable viral shedding and seroconversion observed following aerosol exposure. The optimized system represents a domestically developed approach that may complement existing aerosol exposure platforms, addressing challenges related to accessibility and cost. This study provides preliminary evidence supporting the feasibility of this approach for respiratory infectious disease research, with potential applications in vaccine development and pandemic preparedness.

Bangladesh has historically maintained a low-level human immunodeficiency virus (HIV) epidemic; however, recent surveillance indicates a shifting burden toward men who have sex with men (MSM). This study aimed to assess temporal trends and comparative HIV risk among key populations in Bangladesh. National HIV surveillance data from 2016 to 2025 were analyzed using univariate logistic and Poisson regression models. MSM showed a markedly higher risk (odds ratio [OR] = 5.89; 95% confidence interval [CI]: 5.05-6.90; P < 0.001) of HIV infection compared with people who inject drugs and a significantly higher incidence rate (log-incidence rate ratio [IRR] = 1.2, 95% CI: 1.1-1.3; P < 0.001). Temporal analysis revealed a steep increase in HIV risk among MSM, with odds rising from 2.20 in 2020 to 15.2 in 2025 relative to 2019. These findings indicate an emerging concentrated HIV epidemic among MSM in Bangladesh, underscoring the need for strengthened, context-specific prevention strategies, particularly considering known socio-structural barriers.

The ongoing evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has compromised the efficacy of many neutralizing antibodies. Receptor-mimicking antibodies, whose binding modes partially resemble those of angiotensin-converting enzyme 2 (ACE2), are of particular interest as they recognize functionally constrained regions of the receptor-binding domain (RBD). However, whether these antibodies retain activity against newly emerged SARS-CoV-2 variants remains unclear. In this study, two representative receptor-mimicking antibodies, VIR-7229 and S2K146, were evaluated alongside S2H13, another RBD-targeting antibody. VIR-7229 and S2K146 retained neutralizing activity better than S2H13, with VIR-7229 showing the greatest retention. VIR-7229 potently neutralized the Wuhan-Hu-1, BA.1, XBB.1.5, and BA.2.86 variants and exhibited reduced yet considerable neutralizing activity against KP.3.1.1, XEC, and XEC.25.1. Enzyme-linked immunosorbent assay (ELISA) and biolayer interferometry further demonstrated that VIR-7229 maintained strong binding to spike proteins from recent variants. Computational structural analysis suggested that mutations in these variants may weaken VIR-7229 binding to the RBD but do not fully disrupt the antibody-RBD interface. These findings indicate that VIR-7229 retains considerable neutralizing activity and robust spike recognition against recent SARS-CoV-2 variants, likely through recognition of a functional interface involved in ACE2 binding. This study supports further evaluation of receptor-mimicking antibodies and may inform the design of candidate immunogens against evolving SARS-CoV-2 variants.

Human respiratory syncytial virus (RSV) remains a leading cause of lower respiratory tract illness (LRTI) in infants, young children, and the elderly. Although long-acting monoclonal antibodies, subunit, and messenger ribonucleic acid (mRNA) vaccines can protect vulnerable populations (infants < 6 months old and older adults) via passive and active immunization, respectively, a conspicuous protection gap remains for RSV-seronegative infants and young children aged 6 to 60 months, leaving this vulnerable pediatric cohort largely unprotected. For these RSV-seronegative pediatric populations, intranasal live-attenuated vaccines (LAVs) have emerged as promising formulations owing to the key advantage of lacking vaccine-associated enhanced respiratory disease (VAERD) following natural RSV infection in vaccine recipients. Furthermore, intranasal RSV LAVs can induce the full spectrum of protective immune responses against the virus systemically and locally, including neutralizing antibodies, secretory IgA (SIgA), and tissue-resident memory CD8+ T (TRM) cells. Despite the suboptimal Phase 3 efficacy of Sanofi's RSVt candidate (RSV/ΔNS2/Δ1313/I1314L), alternative RSV LAVs featuring the M2-2 gene deletions have shown enhanced efficacy in clinical studies, alongside emerging strategies designed to rationally augment the immunogenicity of RSV LAVs. Due to the sustained efforts over the past five decades on RSV LAVs, significant advances have been made both in the technology to generate RSV LAVs—most notably reverse genetics—and in our understanding of pivotal benchmarks, including attenuation design, evaluation criteria for attenuation and immune efficacy, as well as the stepwise strategy for clinical research in RSV-seronegative children. Concurrently, this review provides a comprehensive synthesis of these historical and ongoing efforts, while highlighting future directions to prevent RSV disease in RSV-seronegative pediatric populations.