A class of alleles at the VNTR (variable number of tandem repeat) locus in the 5' region of the insulin gene (INS) on chromosome 11p is associated with increased risk of insulin-dependent diabetes mellitus (IDDM), but family studies have failed to demonstrate linkage. INS is thought to contribute to IDDM susceptibility but this view has been difficult to reconcile with the lack of linkage evidence. We thus investigated polymorphisms of INS and neighbouring loci in random diabetics, IDDM multiplex families and controls. HLA-DR4-positive diabetics showed an increased risk associated with common variants at polymorphic sites in a 19-kilobase segment spanned by the 5' INS VNTR and the third intron of the gene for insulin-like growth factor II (IGF2). As INS is the major candidate gene from this region, diabetic and control sequence were compared to identify all INS polymorphisms that could contribute to disease susceptibility. In multiplex families the IDDM-associated alleles were transmitted preferentially to HLA-DR4-positive diabetic offspring from heterozygous parents. The effect was strongest in paternal meioses, suggesting a possible role for maternal imprinting. Our results strongly support the existence of a gene or genes affecting HLA-DR4 IDDM susceptibility which is located in a 19-kilobase region of INS-IGF2. Our results also suggest new ways to map susceptibility loci in other common diseases.

HBsAg-1018 had a similar safety profile to HBsAg-Eng. With improved immunogenicity and fewer doses over a shorter time, HBsAg-1018 has the potential to provide improved seroprotection and a significant public health benefit to adults 18 years of age or older.

Coronavirus disease 2019 (COVID-19) vaccine development and manufacturing have proceeded at a historically unprecedented pace. This speed may be accounted for by the unprecedented scale of resources being devoted to addressing COVID-19; an unusual intensity of cooperation, encompassing the public and private sectors and occurring both within and across national borders; and innovation with respect to both technologies (for example, new vaccine platforms) and processes (for example, vaccine clinical trials). In this article we describe and analyze how resources, cooperation, and innovation have contributed to the accelerated development of COVID-19 vaccines. Similar levels and types of public investment, models of cooperation, and harnessing of innovative processes and technologies could be applied to future epidemics and other global health challenges. P rogress toward the successful development and manufacture of effective coronavirus disease 2019 (COVID-19) vaccines has taken place with remarkable speed. In early December 2020 several national regulatory authorities, including the Food and Drug Administration (FDA), granted emergency or full authorization for a messenger RNA (mRNA) vaccine developed by BioNTech and Pfizer, following review of results from Phase III clinical trials. These determinations were quickly followed by FDA Emergency Use Authorization for a second mRNA vaccine developed by Moderna and the National Institutes of Health (NIH) in the US. Top US public health officials have predicted that hundreds of millions of doses of multiple COVID-19 vaccines will be available to the US population by the second half of 2021. 1 The World Health Organization (WHO) has also suggested that widespread vaccination could take place internationally on a similar timeline, 2 although initial delivery has progressed slowly in a number of high-income settings, including the US. Considering the potential for further delay in remaining clinical trials, regulatory approval, manufacturing, and distribution, it is perhaps more reasonable to project that substantial global access to COVID-19 vaccination may be achieved sometime between 2022 and 2024. Competition among (wealthy) countries to secure sufficient supplies of vaccine for their populations with ample room for contingencies may also contribute to slowing global access. Even so, the rapidity with which both development and, likely, access to COVID-19 vaccines has occurred or is anticipated to occur is entirely without precedent. By comparison, development of the mumps vaccine, which holds the current speed record, took four years from isolation of the mumps virus to licensure in 1967. 3 Indeed, vaccine research and development, manufacturing, and delivery typically involves a long, deliberate process that takes a decade or more (see

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