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Background: SARS-CoV-2 booster vaccination should ideally enhance protection against variants and minimise immune imprinting. This Phase I trial evaluated two vaccines targeting SARS-CoV-2 beta-variant receptor-binding domain (RBD): a recombinant dimeric RBD-human IgG 1 F c -fusion protein, and an mRNA encoding a membrane-anchored RBD., Methods: 76 healthy adults aged 18-64 y, previously triple vaccinated with licensed SARS-CoV-2 vaccines, were randomised to receive a 4th dose of either an adjuvanted (MF59®, CSL Seqirus) protein vaccine (5, 15 or 45 μg, N = 32), mRNA vaccine (10, 20, or 50 μg, N = 32), or placebo (saline, N = 12) at least 90 days after a 3rd boost vaccination or SARS-CoV-2 infection. Bleeds occurred on days 1 (prior to vaccination), 8, and 29., Clinicaltrials: govNCT05272605., Findings: No vaccine-related serious or medically-attended adverse events occurred. The protein vaccine reactogenicity was mild, whereas the mRNA vaccine was moderately reactogenic at higher dose levels. Best anti-RBD antibody responses resulted from the higher doses of each vaccine. A similar pattern was seen with live virus neutralisation and surrogate, and pseudovirus neutralisation assays. Breadth of immune response was demonstrated against BA.5 and more recent omicron subvariants (XBB, XBB.1.5 and BQ.1.1). Binding antibody titres for both vaccines were comparable to those of a licensed bivalent mRNA vaccine. Both vaccines enhanced CD4 + and CD8 + T cell activation., Interpretation: There were no safety concerns and the reactogenicity profile was mild and similar to licensed SARS-CoV-2 vaccines. Both vaccines showed strong immune boosting against beta, ancestral and omicron strains., Funding: Australian Government Medical Research Future Fund, and philanthropies Jack Ma Foundation and IFM investors., Competing Interests: Declaration of interests The vaccines evaluated in this Phase I study were the result of independent University of Melbourne and Monash University research and development, with funding provided by the Australian Government's Medical Research Future Fund (MRFF), the National Health and Medical Research Council (NHMRC), the Victorian Government (mRNA Victoria) and philanthropic funders. The MF59 for the protein-RBD candidate was donated by CSL Seqirus. One author (S.R.) is an employee of CSL Seqirus and he also has an adjunct (honorary) appointment to the University of Melbourne. G.D., N.G., D.P., D.I.G. are named inventors on 2 provisional patents for the RBD-Fc dimer vaccine in this study. T.M.N. has been a DSMB member for vaccine studies conducted by Moderna, Clover, Novavax, CSL Seqirus, and SK Bioscience Korea, and has received payment for advisory roles on vaccines from AstraZeneca, Moderna, MSD, Sanofi, CSL, and Pfizer. G.D. received salary support from philanthropic funds from IFM Investors Pty Ltd. S.L. received consulting fees from several companies related to HIV research, and honoraria from MSD and Gilead. H.McQ. received consulting fees from Ena Respiratory Pty Ltd. K.S. was a member of a DSMB for a vaccine study in Thailand. H.alW. received consulting and research funding from CSL Seqirus. D.I.G. received research support from CSL., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

High-risk groups, including Indigenous people, are at risk of severe COVID-19. Here we found that Australian First Nations peoples elicit effective immune responses to COVID-19 BNT162b2 vaccination, including neutralizing antibodies, receptor-binding domain (RBD) antibodies, SARS-CoV-2 spike-specific B cells, and CD4 + and CD8 + T cells. In First Nations participants, RBD IgG antibody titers were correlated with body mass index and negatively correlated with age. Reduced RBD antibodies, spike-specific B cells and follicular helper T cells were found in vaccinated participants with chronic conditions (diabetes, renal disease) and were strongly associated with altered glycosylation of IgG and increased interleukin-18 levels in the plasma. These immune perturbations were also found in non-Indigenous people with comorbidities, indicating that they were related to comorbidities rather than ethnicity. However, our study is of a great importance to First Nations peoples who have disproportionate rates of chronic comorbidities and provides evidence of robust immune responses after COVID-19 vaccination in Indigenous people., (© 2023. The Author(s).)

Purpose: Carrier screening (CS) is a term used to describe a genetic test performed on individuals without family history of genetic disorders, to investigate the carrier status for pathogenic variants associated with multiple recessive conditions. The advent of next-generation sequencing enabled simultaneous CS for an increasing number of conditions; however, a consensus on which diseases to include in gene panels and how to best develop the provision of CS is far to be reached. Therefore, the provision of CS is jeopardized and inconsistent and requires solving several important issues., Methods: In 2020, the Italian Society of Human Genetics (SIGU) established a working group composed of clinical and laboratory geneticists from public and private fields to elaborate a document to define indications and best practice of CS provision for couples planning a pregnancy., Results: Hereby, we present the outcome of the Italian working group's activity and compare it with previously published international recommendations (American College of Medical Genetics and Genomics (ACMG), American College of Obstetricians and Gynecologists (ACOG), and Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG)). We determine a core message on genetic counseling and nine main subject categories to explore, spanning from goals and execution to technical scientific, ethical, and socio-economic topics. Moreover, a level of agreement on the most critical points is discussed using a 5-point agreement scale, demonstrating a high level of consensus among the four societies., Conclusions: This document is intended to provide genetic and healthcare professionals involved in human reproduction with guidance regarding the clinical implementation of CS., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: As vaccines against SARS-CoV-2 are now being rolled out, a better understanding of immunity to the virus, whether from infection, or passive or active immunisation, and the durability of this protection is required. This will benefit from the ability to measure antibody-based protection to SARS-CoV-2, ideally with rapid turnaround and without the need for laboratory-based testing., Methods: We have developed a lateral flow POC test that can measure levels of RBD-ACE2 neutralising antibody (NAb) from whole blood, with a result that can be determined by eye or quantitatively on a small instrument. We compared our lateral flow test with the gold-standard microneutralisation assay, using samples from convalescent and vaccinated donors, as well as immunised macaques., Findings: We show a high correlation between our lateral flow test with conventional neutralisation and that this test is applicable with animal samples. We also show that this assay is readily adaptable to test for protection to newly emerging SARS-CoV-2 variants, including the beta variant which revealed a marked reduction in NAb activity. Lastly, using a cohort of vaccinated humans, we demonstrate that our whole-blood test correlates closely with microneutralisation assay data (specificity 100% and sensitivity 96% at a microneutralisation cutoff of 1:40) and that fingerprick whole blood samples are sufficient for this test., Interpretation: Taken together, the COVID-19 NAb-test TM device described here provides a rapid readout of NAb based protection to SARS-CoV-2 at the point of care., Funding: Support was received from the Victorian Operational Infrastructure Support Program and the Australian Government Department of Health. This work was supported by grants from the Department of Health and Human Services of the Victorian State Government; the ARC (CE140100011, CE140100036), the NHMRC (1113293, 2002317 and 1116530), and Medical Research Future Fund Awards (2005544, 2002073, 2002132). Individual researchers were supported by an NHMRC Emerging Leadership Level 1 Investigator Grants (1194036), NHMRC APPRISE Research Fellowship (1116530), NHMRC Leadership Investigator Grant (1173871), NHMRC Principal Research Fellowship (1137285), NHMRC Investigator Grants (1177174 and 1174555) and NHMRC Senior Principal Research Fellowships (1117766 and 1136322). Grateful support was also received from the A2 Milk Company and the Jack Ma Foundation., Competing Interests: Declaration of Competing Interest A provisional patent covering the COVID-19 NAb-test(TM) test and underlying technology has been submitted through The University of Melbourne. Dr. Fulford reports a patent Australian Provisional Patent Application 2021901011 (filed 7 April 2021) “Point of care lateral flow test for COVID19 detection” pending. Mr. Van reports grants from Government of the State of Victoria, during the conduct of the study; In addition, Mr. Van has a patent Australian Provisional Patent Application 2021901011 (filed 7 April 2021) “Point of care lateral flow test for COVID19 detection” pending. Dr. Gherardin reports a patent Australian Provisional Patent Application 2021901011 (filed 7 April 2021) “Point of care lateral flow test for COVID19 detection” pending. Ms. Zheng reports grants from Government of the State of Victoria, during the conduct of the study; In addition, Ms. Zheng has a patent Australian Provisional Patent Application 2021901011 (filed 7 April 2021) “Point of care lateral flow test for COVID19 detection” pending. Mr. Ciula has nothing to disclose. Prof. Drummer has nothing to disclose. Mr. Redmond has nothing to disclose. Dr. Tan has nothing to disclose. Ms. Boo has nothing to disclose. Dr. Center has nothing to disclose. Dr. Li has nothing to disclose. Dr. Grimley has nothing to disclose. Dr. Wines reports grants from Australian Govt, Medical Research Future Fund, grants from NHMRC, National Health and Medical Research Council GNT1145303, Australia, during the conduct of the study; In addition, Dr. Wines has a patent drafted for use of ACE2-Fc pending. Dr. Nguyen has nothing to disclose. Ms. Mordant has nothing to disclose. Dr. Ellenberg has nothing to disclose. Dr. Rowntree has nothing to disclose. Lukasz Kedzierski has nothing to disclose. Prof. Cheng reports that he is a member of government advisory committees advising on COVID policy. Prof. Doolan has nothing to disclose. Prof. Matthews reports grants from Curran Foundation, during the conduct of the study; grants from Gilead sciences, grants from Abbvie Inc outside the submitted work. Dr. Bond has nothing to disclose. Prof. Hogarth reports grants from NHMRC, grants from MRFF, during the conduct of the study; In addition, Prof. Hogarth has a patent Antiviral pending. A/Prof. McQuilten reports grants from Medical Research Future Fund, during the conduct of the study. Prof. Subbarao has nothing to disclose. Prof. Kedzierska has nothing to disclose. Dr. Juno has nothing to disclose. Dr. Wheatley has nothing to disclose. Prof. Kent has nothing to disclose. Prof. Williamson has nothing to disclose. Prof. Purcell reports grants from Victorian Government DHHS, grants from Medical Research Future Fund, other from Jack Ma Foundation, during the conduct of the study; In addition, Prof. Purcell has a patent PCT/AU2021/050839 pending. Prof. Anderson reports grants from Government of the State of Victoria, during the conduct of the study; other from Nanjing BioPoint Diagnostic Technology, outside the submitted work; In addition, Prof. Anderson has a patent Australian Provisional Patent Application 2021901011 (filed 7 April 2021) “Point of care lateral flow test for COVID19 detection” pending. Prof. Godfrey reports grants from Victorian Government DHHS, and from Australian Research Council, during the conduct of the study; grants from Medical Research Future Fund, other from Jack Ma Foundation, grants from National Health and Medical Research Council, outside the submitted work; In addition, Prof. Godfrey has a patent Australian Provisional Patent Application 2021901011 (filed 7 April 2021) “Point of care lateral flow test for COVID19 detection” pending., (Copyright © 2021. Published by Elsevier B.V.)