Hepatitis E virus (HEV) remains a leading cause of acute viral hepatitis globally, particularly in South Asia and Africa. However, epidemiological prioritization is hampered by fragmented data and discordant disease burden estimates. Following JBI and PRISMA-Sc guidelines, we conducted a scoping review of global HEV evidence. We used the PCC framework: (P) general and high-risk populations (pregnant women, immunocompromised, and displaced groups); (C) quantitative estimates of burden, risk factors, or virological gaps; and (C) global evidence across all WHO regions to include studies. We searched PubMed, Scopus, and Web of Science, supplemented by country-specific searches in Google Scholar and IHME. From 11,583 citations, 395 articles met the inclusion criteria. The temporal distribution shows a marked increase in research volume, with 65.3% of studies published after 2010; however, 54.9% relied on observational descriptive designs while experimental investigations remained infrequent (4.3%). We identified three estimates of the global burden of HEV: the IHME Global Burden of Disease (GBD) published in 2021 (19.4 million cases) and two widely cited systematic reviews published in 2012 (20.1 million infections) and 2020 (939 million infections). A significant virological "blind spot" was observed, as 47.8% of studies did not report genotype information, though Genotype 3 (21.8%) was the most frequently identified among specified reports. Key risk domains identified were environmental (sanitation/water contamination) and cultural/occupational practices. Pregnant women, immunocompromised patients, and patients with pre-existing liver conditions were high at-risk populations. Key knowledge gaps identified were limited confidence in burden of disease estimates: severe molecular blind spots and evidence deserts, limited public health resources for surveillance, diagnostics, and reporting of cases and deaths in highest risk settings; exclusion of outbreaks from estimates of the burden of disease and unreliable convenience sample derived estimates. Hepatitis E virus is often neglected by international communities, global actors and national governments. However, it is difficult for stakeholders to prioritize a pathogen with highly variable and unreliable global burden of disease estimates. Comprehensive country level data based on more access to routine testing could facilitate global initiatives to devise strategies for equitable vaccination and mitigate the morbidity and mortality associated with this vaccine-preventable disease.
BACKGROUND:Human adenovirus type 55 (hAd55) infection can lead to acute respiratory diseases that often present with severe symptoms. Despite its persistent prevalence in military camps and communities, there are no commercially available vaccines or vaccine candidates undergoing clinical evaluation; therefore, there is an urgent need to address this. In this study, we evaluated the immunogenicity of inactivated hAd55 isolates and investigated the effects of adjuvants and various immunization intervals. METHODS AND RESULTS:To select a vaccine candidate, four hAd55 strains (6-9, 6-15 (AFMRI 41014), 28-48 (AFMRI 41013), and 12-164 (AFMRI 41012)) were isolated from infected patients in military camps. Sequence analysis revealed no variation in the coding regions of structural proteins, including pentons, hexons, and fibers. Immunization with inactivated hAd55 isolates elicited robust hAd55-specific binding and neutralizing antibody responses in mice, with adjuvants, particularly alum hydroxide (AH), enhancing antibody titers. Co-immunization with AH also induced hAd14-specific neutralizing antibody responses but did not induce hAd11-specific neutralizing antibody responses. Notably, booster immunization administered at a four-week interval resulted in superior immune responses compared with shorter immunization intervals. CONCLUSIONS:Prime-boost immunization with the inactivated hAd55 isolate and an AH adjuvant shows promise as a potential approach for preventing hAd55-induced respiratory disease. Further research is needed to evaluate the efficacy and safety of these vaccine candidates in preventing hAd55-associated respiratory illnesses.
African swine fever virus (ASFV) causes a fatal hemorrhagic disease in domestic pigs and wild boars, which poses severe threats to the global pork industry. Despite the promise of live attenuated vaccines (LAVs), their narrow margin between efficacy and residual virulence presents major safety challenges. This study bridges a critical knowledge gap in ASF vaccinology by identifying innate and adaptive correlates of protection. This was achieved by using an established model with two groups of pigs differing in baseline immunological status (farm and specific pathogen-free [SPF]). The animals were immunized with an attenuated ASFV strain and subsequently challenged with a related, highly virulent genotype II strain. By applying a systems immunology approach, we correlated kinetic data, including serum cytokines, blood transcription modules (BTMs), T-cell responses, and antibody levels, with clinical outcomes to track protective and detrimental immune responses to the virus over time. Key innate correlates of protection included early and sustained IFN-α response, activation of antigen presentation BTMs, and controlled IL-8 levels during immunization. Lower baseline immune activation observed in SPF pigs in steady state was linked to increased protection. Adaptive correlates encompassed cell cycle, plasma cell, and T-cell BTM responses lasting until day 15 post-immunization. Consequently, an effective response from ASFV-specific Th cells prior to challenge indicated protection. After the challenge, an early IFN-α response, along with low levels of pro-inflammatory cytokines and a strong induction of memory Th and Tc cells, correlated with improved clinical outcomes. The model highlights the critical role of host-specific factors in vaccine efficacy and provides a valuable framework for optimizing ASFV vaccine design while distinguishing between protective and detrimental immune responses.
