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Abstract:It is necessary to understand whether some humans possess natural humoral-immune protection for avian-H5N1 influenza. To broadly assess an exposure naïve cohort we have examined intravenous immunoglobulins (IVIGs) isolated from pools of many thousands of normal Australian blood donations. In studies of the anti-H5N1 antibody potential of these highly purified IVIG therapeutics and of individual donor sera we have identified antibodies that bind to both H5N1 surface envelope and internal viral proteins and neutralize in vitro MDCK and Vero cell infections by highly pathogenic avian influenza clade I and II and human-derived H5N1 isolates. As this reactivity is removed by adsorption with purified H3N2 and H1N1 strains, anti-H5N1 cross-reacting hetero-typic antibodies are implicated. These findings support that some individuals do contain low levels of specific and neutralizing anti-H5N1 antibodies. The protective relevance of this in vivo remains yet to be determined.

With antigenically novel epidemic and pandemic influenza strains persistently on the horizon it is of fundamental importance that we understand whether heterosubtypic antibodies gained from exposures to circulating human influenzas exist and can protect against emerging novel strains. Our studies of IVIG obtained from an infection-naive population (Australian) enabled us to reveal heterosubtypic influenza antibodies that cross react with H5N1. We now expand those findings for an Australian donor population to include IVIG formulations from a variety of northern hemisphere populations. Examination of IVIGs from European and South East-Asian (Malaysian) blood donor populations further reveal heterosubtypic antibodies to H5N1 in humans from different global regions. Importantly these protect against highly pathogenic avian H5N1 infection in vitro, albeit at low titres of inhibition. Although there were qualitative and quantitative differences in binding and protection between globally different formulations, the heterosubtypic antibody activities for the respective IVIGs were in general quite similar. Of particular note because of the relative geographic proximity to the epicentre of H5N1 and the majority of human infections, was the similarity in the antibody binding responses between IVIGs from the Malayan peninsula, Europe and Australia. These findings highlight the value of employing IVIGs for the study of herd immunity, and particularly heterosubtypic antibody responses to viral antigens such as those conserved between circulating human influenzas and emerging influenza strains such as H5N1. They also open a window into a somewhat ill defined arena of antibody immunity, namely heterosubtypic immunity.

Introduction Pregnant women are at higher risk of severe illness from coronavirus disease 2019 (COVID‐19) than non‐pregnant women of a similar age. Early in the COVID‐19 pandemic, it was clear that evidenced‐based guidance was needed, and that it would need to be updated rapidly. The National COVID‐19 Clinical Evidence Taskforce provided a resource to guide care for people with COVID‐19, including during pregnancy. Care for pregnant and breastfeeding women and their babies was included as a priority when the Taskforce was set up, with a Pregnancy and Perinatal Care Panel convened to guide clinical practice. Main recommendations As of May 2022, the Taskforce has made seven specific recommendations on care for pregnant women and those who have recently given birth. This includes supporting usual practices for the mode of birth, umbilical cord clamping, skin‐to‐skin contact, breastfeeding, rooming‐in, and using antenatal corticosteroids and magnesium sulfate as clinically indicated. There are 11 recommendations for COVID‐19‐specific treatments, including conditional recommendations for using remdesivir, tocilizumab and sotrovimab. Finally, there are recommendations not to use several disease‐modifying treatments for the treatment of COVID‐19, including hydroxychloroquine and ivermectin. The recommendations are continually updated to reflect new evidence, and the most up‐to‐date guidance is available online ( https://covid19evidence.net.au ). Changes in management resulting from the guidelines The National COVID‐19 Clinical Evidence Taskforce has been a critical component of the infrastructure to support Australian maternity care providers during the COVID‐19 pandemic. The Taskforce has shown that a rapid living guidelines approach is feasible and acceptable.