Thomas Tipih

The highly pathogenic avian influenza (HPAI) A(H5N1) clade 2.3.4.4b viruses, responsible for the current outbreak in dairy cows in the United States, pose a significant animal and public health threat. In this study, we compare disease progression and pathology of three recent clade 2.3.4.4b isolates derived from a cow, a mountain lion, and a mink to a human HPAI A(H5N1) isolate from Vietnam in mice. Inoculating C57BL/6J and BALB/c mice with all four HPAI A(H5N1) isolates results in comparable levels of virus replication in the lung inducing significant local pro-inflammatory cytokine responses and severe respiratory disease. Infecting C57BL/6J mice with the bovine isolate yields high viral titers in the brain, a significant pro-inflammatory cytokine response and neurologic disease. Our findings suggest the recent bovine isolate possesses enhanced neuroinvasive/neurovirulent disease causing fatal respiratory and neurologic disease in C57BL/6J mice.

Since early 2022 highly pathogenic avian influenza (HPAI) H5N1 virus infections have been reported in wild aquatic birds and poultry throughout the United States (US) with spillover into several mammalian species^1-6. In March 2024, HPAIV H5N1 clade 2.3.4.4b was first detected in dairy cows in Texas, US and continues to circulate on dairy farms in multiple states^7,8. Milk production and quality are diminished in infected dairy cows, with high virus titers in milk raising concerns of exposure to mammals including humans through consumption^9-12. Here we investigated routes of infection with bovine HPAIV H5N1 clade 2.3.4.4b in cynomolgus macaques, a surrogate model for human infection¹³. We show that intranasal or intratracheal inoculation of macaques could cause systemic infection resulting in mild and severe respiratory disease, respectively. In contrast, infection by the orogastric route resulted in limited infection and seroconversion of macaques which remained subclinical.

The ongoing circulation of influenza A H5N1 in the United States has raised concerns of a pandemic caused by highly pathogenic avian influenza. Although the United States has stockpiled and is prepared to produce millions of vaccine doses to address an H5N1 pandemic, currently circulating H5N1 viruses contain multiple mutations within the immunodominant head domain of hemagglutinin (HA) compared to the antigens used in stockpiled vaccines. It is unclear if these stockpiled vaccines will need to be updated to match the contemporary H5N1 strains. Here we show that a replicating RNA vaccine expressing the HA of an H5N1 isolated from a US dairy cow confers complete protection against homologous lethal challenge in mice. A repRNA encoding the HA of a clade 1 H5 from 2004 (A/Vietnam/1203/2004) as utilized by some stockpiled vaccines, confers only partial protection. Our data highlight the utility of nucleic acid vaccines to be rapidly updated to match emergent viruses of concern while demonstrating that contemporary bovine H5N1 viruses can evade immunity elicited by historical HA antigens.

Since early 2022 highly pathogenic avian influenza (HPAI) H5N1 virus infections have been reported in wild aquatic birds and poultry throughout the United States (US) with spillover into several mammalian species1-6. In March 2024, HPAIV H5N1 clade 2.3.4.4b was first detected in dairy cows in Texas, US currently affecting more than 190 dairy farms in 14 states7,8. Milk production and quality are diminished in infected dairy cows, with high virus titers in milk raising concerns of exposure through consumption9-12. Here we investigated routes of infection with HPAIV H5N1 clade 2.3.4.4b in cynomolgus macaques, a surrogate model for human infection13. We show that intranasal or intratracheal inoculation of macaques caused systemic infection resulting in mild and severe respiratory disease, respectively. In contrast, infection by the orogastric route resulted in limited infection and seroconversion of macaques which remained subclinical. The study shows that consumption of contaminated products, such as milk, may lead to self-limiting, subclinical infection in primates.

The highly pathogenic avian influenza (HPAI) A(H5N1) clade 2.3.4.4b viruses, responsible for the current outbreak in dairy cows in the United States, pose a significant animal and public health threat. In this study, we compared disease progression and pathology of three recent clade 2.3.4.4b isolates derived from a cow, mountain lion, and mink to a human HPAI A(H5N1) isolate from Vietnam in mice. Inoculation of C57BL/6J and BALB/c mice with all four HPAI A(H5N1) isolates resulted in comparable levels of virus replication in the lung inducing severe respiratory disease. C57BL/6J mice infected with the bovine isolate also developed high virus titers in the brain, resulting in a significant pro-inflammatory cytokine response and neurologic disease. Our findings suggest the recent bovine isolate possesses enhanced respiratory and neuroinvasive/neurovirulent properties causing fatal respiratory and neurologic disease in C57BL/6J mice.

Crimean–Congo hemorrhagic fever virus (CCHFV) infrequently causes hemorrhagic fever in humans with a case fatality rate of 30%. Currently, there is neither an internationally approved antiviral drug nor a vaccine against the virus. A replicon based on the Sindbis virus vector encoding the complete open reading frame of a CCHFV nucleoprotein from a South African isolate was prepared and investigated as a possible candidate vaccine. The transcription of CCHFV RNA and recombinant protein production by the replicon were characterized in transfected baby hamster kidney cells. A replicon encoding CCHFV nucleoprotein inserted in plasmid DNA, pSinCCHF-52S, directed transcription of CCHFV RNA in the transfected cells. NIH-III heterozygous mice immunized with pSinCCHF-52S generated CCHFV IgG specific antibodies with notably higher levels of IgG2a compared to IgG1. Splenocytes from mice immunized with pSinCCHF-52S secreted IFN-γ and IL-2, low levels of IL-6 or IL-10, and no IL-4. No specific cytokine production was registered in splenocytes of mock-immunized mice (p < 0.05). Thus, our study demonstrated the expression of CCHFV nucleoprotein by a Sindbis virus vector and its immunogenicity in mice. The spectrum of cytokine production and antibody profile indicated predominantly Th1-type of an anti-CCHFV immune response. Further studies in CCHFV-susceptible animals are necessary to determine whether the induced immune response is protective.

Aim: The aim of this study was to investigate the utility of serological tests for the diagnosis of COVID-19 during the first week of symptom onset in patients confirmed with the real-time RT-PCR. ...

COVID-19 has plagued the world since it was first identified in December 2019. Previous systematic reviews and meta-analysis were limited by various factors such as the usage of non-peer reviewed data and were also limited by the lack of clinical data on a global scale.