Single MVA-SARS-2-ST/N Vaccination Rapidly Protects K18-hACE2 Mice against a Lethal SARS-CoV-2 Challenge Infection.

The sudden emergence of SARS-CoV-2 demonstrates the need for new vaccines that rapidly protect in the case of an emergency. In this study, we developed a recombinant MVA vaccine co-expressing SARS-CoV-2 prefusion-stabilized spike protein (ST) and SARS-CoV-2 nucleoprotein (N, MVA-SARS-2-ST/N) as an approach to further improve vaccine-induced immunogenicity and efficacy. Single MVA-SARS-2-ST/N vaccination in K18-hACE2 mice induced robust protection against lethal respiratory SARS-CoV-2 challenge infection 28 days later. The protective outcome of MVA-SARS-2-ST/N vaccination correlated with the activation of SARS-CoV-2-neutralizing antibodies (nABs) and substantial amounts of SARS-CoV-2-specific T cells especially in the lung of MVA-SARS-2-ST/N-vaccinated mice. Emergency vaccination with MVA-SARS-2-ST/N just 2 days before lethal SARS-CoV-2 challenge infection resulted in a delayed onset of clinical disease outcome in these mice and increased titers of nAB or SARS-CoV-2-specific T cells in the spleen and lung. These data highlight the potential of a multivalent COVID-19 vaccine co-expressing S- and N-protein, which further contributes to the development of rapidly protective vaccination strategies against emerging pathogens.

Single Nucleotide Polymorphisms Associated with AA-Amyloidosis in Siamese and Oriental Shorthair Cats.

AA-amyloidosis in Siamese and Oriental shorthair cats is a lethal condition in which amyloid deposits accumulate systemically, especially in the liver and the thyroid gland. The age at death of affected cats varies between one and seven years. A previous study indicated a complex mode of inheritance involving a major locus. In the present study, we performed a multi-locus genome-wide association study (GWAS) using five methods (mrMLM, FASTmrMLM, FASTmrEMMA, pLARmEB and ISIS EM-BLASSO) to identify variants associated with AA-amyloidosis in Siamese/Oriental cats. We genotyped 20 affected mixed Siamese/Oriental cats from a cattery and 48 healthy controls from the same breeds using the Illumina Infinium Feline 63 K iSelect DNA array. The multi-locus GWAS revealed eight significantly associated single nucleotide polymorphisms (SNPs) on FCA A1, D1, D2 and D3. The genomic regions harboring these SNPs contain 55 genes, of which 3 are associated with amyloidosis in humans or mice. One of these genes is SAA1, which encodes for a member of the Serum Amyloid A family, the precursor protein of Amyloid A, and a mutation in the promotor of this gene causes hereditary AA-amyloidosis in humans. These results provide novel knowledge regarding the complex genetic background of hereditary AA-amyloidosis in Siamese/Oriental cats and, therefore, contribute to future genomic studies of this disease in cats.