ETIDIOH - NEW

ABSTRACT Betacoronaviruses, which have caused three human outbreaks within the last two decades, are thought to originate from bats , raising the concern that bat coronaviruses could cause a novel human outbreak in the future. To determine whether the bat merbecovirus EjCoV-3 strain , previously detected in Eptesicus japonensis in Japan , has the potential to infect humans, we analyzed its cellular entry mechanism. Cellular entry of EjCoV-3 via the spike protein requires protease treatment and is mediated by an unknown receptor, other than DPP4 or ACE2 . We generated cultivable recombinant EjCoV-3 using bacterial artificial chromosome-based reverse genetics and found that it efficiently replicated in human respiratory and intestinal cell cultures as well as nasal ciliated epithelium in hamsters. These findings suggest that bat merbecovirus with ACE2- and DPP4-independent cell entry has the potential to cause human infections , highlighting the importance of extensive bat surveillance f...

Highlights •  Systematic and routine monitoring antigenic drift and shift of AIV in wild birds and poultry is needed. •  Community-based surveillance is key for improving NiV case detection. •  Integrated surveillance across One Health sectors is required. •  Lab upgrades to BSL-3 are needed for enhanced biosafety and diagnostics. Abstract Nipah and avian influenza viruses (NiV and AIV) are priority zoonotic pathogens in Bangladesh and are also important globally because of their pandemic potential . To understand current strengths, areas for improvement, and opportunities to enhance preparedness for NiV and AIV in Bangladesh, as part of the USAID STOP Spillover program , 47 relevant stakeholders were surveyed, and two country leads of the primary surveillance systems were interviewed. Data was collected focusing on four different areas: research projects, surveillance systems, laboratories, and outbreak risk management systems. Despite progress in recent years, our ...

Agreement’s adoption follows three years of intensive negotiation launched due to gaps and inequities identified in national and global COVID-19 response. Agreement boosts global collaboration to ensure stronger , more equitable response to future pandemics. Next steps include negotiations on Pathogen Access and Benefits Sharing system. Member States of the World Health Organization (WHO) today formally adopted by consensus the world's first Pandemic Agreement. The landmark decision by the 78th World Health Assembly culminates more than three years of intensive negotiations launched by governments in response to the devastating impacts of the COVID-19 pandemic, and driven by the goal of making the world safer from – and more equitable in response to – future pandemics. “The world is safer today thanks to the leadership , collaboration and commitment of our Member States to adopt the historic WHO Pandemic Agreement,” said Dr Tedros Adhanom Ghebreyesus, WHO Director-General.  “The Ag...

Abstract Accidental lab–acquired infections (LAIs) risk releasing potential pandemic pathogens (PPPs) from BSL–3/4 facilities . We constructed a stochastic network infectious disease model to simulate how the probability of an outbreak of a pathogen resembling wild–type SARS–COV–2, following an initial LAI would be influenced by test–and–isolate interventions over a 100–day horizon . We varied test frequency (0–7 tests/week), peak sensitivity (50–100%), and isolation delay (0–3 days). For each of 192 parameter combinations, we conducted 1,000 simulations and used logistic regression to quantify how each parameter influenced the likelihood of an outbreak of 50 or more infections. Results indicated that even relatively infrequent routine testing significantly reduced the risk of outbreaks under diverse plausible scenarios, with greater reductions achieved at higher test frequencies. Once-weekly testing reduced outbreak risk by 52% under optimistic assumptions (80% sensitivity, 1–day dela...

Abstract Highly pathogenic avian influenza (HPAI) H5N1 has been a global concern since its emergence in 1997, causing widespread outbreaks in birds and sporadic human infections . The clade 2.3.4.4b H5N1 virus has rapidly expanded across continents, infecting numerous mammalian species . In 2024, it was detected in dairy cattle for the first time in the U.S., along with human cases following exposure . In Canada , the first human case of this avian influenza was reported in a critically ill adolescent in late 2024. No human-to-human transmission has been documented, but concerns persist regarding mutations associated with enhanced virulence and human adaptation . Although seasonal influenza vaccines are not directed against H5N1, studies suggest that pre-existing immunity from prior infections or vaccinations may provide partial protection against severe H5N1 infections through cross-reactive immune response . Given the ongoing circulation of avian influenza and the rise in human infec...

Abstract We tested cross-neutralization against highly pathogenic avian influenza A(H5N1) virus in adults vaccinated with 2021–2023 seasonal quadrivalent influenza vaccine in the United Kingdom. Seasonal quadrivalent influenza vaccines are unlikely to protect vulnerable persons against severe H5N1 disease during widespread transmission. Enhanced measures are needed to protect vulnerable people from H5N1 virus infection. Source: US Centers for Disease Control and Prevention,  https://wwwnc.cdc.gov/eid/article/31/6/24-1796_article ____

ABSTRACT The recent emergence of the H5N1 influenza virus in dairy cattle has raised significant public health concerns . Using a previously established pseudovirus-based neutralization assay , we evaluated the impact of emerging hemagglutinin (HA) mutations on the efficacy of current candidate vaccine viruses (CVVs). Neutralization analysis revealed that the cow-derived H5N1 virus showed up to a 2.2-fold reduction in sensitivity compared to the CVV homologous neutralization titers. Among the 1,453 HA sequences analyzed from cow-derived H5N1 viruses, we identified four major mutations (E2K, D104G, V147M, and S336N) that emerged after the initial isolation, with 134 isolates (9.22%) harboring all four mutations . These multi-mutation variants exhibited up to a 3.3-fold reduction compared with the CVV homologous neutralization titers. Single-mutation analysis demonstrated that the D104G mutation , present in 47.8% of sequences, markedly contributed to antibody escape . Our findings highl...

Abstract The GreVac vaccine technology was created as a fast and flexible plug-and-play vaccine platform based on a 4th generation architecture of fully deleted (fd) helper virus independent (hi) adenoviral (Ad) vectors. For the initial proof-of-principle studies , we at Greffex had engineered an avian influenza vaccine , which delivered a transgene expression cassette for an avian influenza virus H5 hemagglutinin and N1 neuraminidase genes in a capsid of the common human Ad serotype 5 (Ad5). This vaccine proved highly immunogenic and protective in mice . These studies revealed that intramuscular (i.m.) delivery proved more efficient than subcutaneous (s.c.) or intranasal (i.n.) routes. In the human population, pre-exposure to the Ad5 virus is common. To minimize interference by pre-existing anti-Ad5 immunities, we created a new GreVac-based avian influenza vaccine, in which the fd Ad genome was packaged into a capsid of the rare human Ad serotype 6 (Ad6). We now report that at very lo...

Abstract The global spread, frequent antigenic changes, and pandemic potential of clade 2.3.4.4b highly pathogenic avian influenza H5N1 underscore the urgent need for robust cross-protective vaccines . Here, we developed a clade 2.3.4.4b H5N1 whole inactivated virus (WIV) vaccine strain with improved structural stability, productivity, and safety. By analyzing the evolutionary trends of clade 2.3.4.4b H5N1 viruses, we identified a key mutation (R90K) that increases heat stability while preserving antigenicity. Additionally, the PB2 gene of PR8 was replaced with a prototypical avian PB2 gene to increase replication efficiency in embryonated chicken eggs and reduce replication efficiency in mammalian cells, thereby improving productivity and biosafety. We found that our optimized clade 2.3.4.4b H5N1 vaccine strain (22W_KY), inactivated with binary ethylenimine (BEI), had superior antigen internalization into respiratory epithelial cells compared to those inactivated with formaldehyde or ...

At a glance -- The Influenza Risk Assessment Tool (IRAT) is a CDC evaluation tool developed with assistance from global animal and human health influenza experts. -- The IRAT is used to assess the potential pandemic risk of influenza A viruses that are not currently circulating in people. -- This latest IRAT assessed two recent clade 2.3.4.4b avian influenza A(H5N1) viruses: A/California/147/2024 and A/Washington/239/2024. -- These viruses scored in the "moderate risk" category for potential emergence and public health impact , similar to previous assessments of earlier clade 2.3.4.4b avian influenza A(H5N1) viruses. These results validate the proactive, coordinated U.S. government response. -- The IRAT does not assess the immediate risk to the public's health, which is unchanged and remains low, and it does not predict future pandemics. Purpose The IRAT uses expert opinion to evaluate the potential of a representative novel influenza A virus to gain the ability for perso...

Abstract Highly pathogenic avian influenza (HPAI) A(H5N1) clade 2.3.4.4b was first detected in birds in the United States in 2021 and an ongoing outbreak in dairy cattle began in early 2024. At least 70 U.S. cases have been identified in humans with exposure to infected cattle, poultry, and wild birds. No human-to-human transmission has been documented . However, as part of diagnostic preparedness, we evaluated the ability of currently available influenza tests to detect 2024 U.S. H5N1 strains. Contrived nasal swab samples were prepared using live or inactivated 2024 H5N1 and used to test twelve rapid antigen tests (lateral flow assays, or LFA), including 10 commercially-available influenza A LFAs and two H5-specific LFAs. Five point-of-care (POC) molecular assays were also tested. An inclusivity testing protocol was used, wherein a predetermined dilution series is used to evaluate each assay, enabling head-to-head comparison of assay performance. All lateral flow assays and POC molecu...

Key points   -- At the present time , based on available information, FAO-WHO-WOAH assess the global public health risk of influenza A(H5) viruses to be low , while the risk of infection for occupationally exposed persons is low to moderate depending on the risk mitigation measures in place and the local avian influenza epidemiological situation.  -- Transmission between animals continues to occur and, to date, a growing yet still limited number of human infections are being reported. Although additional human infections associated with exposure to infected animals or contaminated environments are expected to occur, the overall public health impact of such infections at a global level, at the present time, is considered minor .  -- The assessment could change if and when additional epidemiological or virological information becomes available.  -- This risk assessment from FAO, WHO and WOAH updates the assessment of the risk of zoonotic transmission (for example, ani...