The SARS-CoV-2 Omicron variant (B.1.1.529) has multiple spike protein mutations^1,2 that contribute to viral escape from antibody neutralization^3–6 and reduce vaccine protection from infection^7,8. The extent to which other components of the adaptive response such as T cells may still target Omicron and contribute to protection from severe outcomes is unknown. Here we assessed the ability of T cells to react to Omicron spike protein in participants who were vaccinated with Ad26.CoV2.S or BNT162b2, or unvaccinated convalescent COVID-19 patients (n = 70). Between 70% and 80% of the CD4⁺ and CD8⁺ T cell response to spike was maintained across study groups. Moreover, the magnitude of Omicron cross-reactive T cells was similar for Beta (B.1.351) and Delta (B.1.617.2) variants, despite Omicron harbouring considerably more mutations. In patients who were hospitalized with Omicron infections (n = 19), there were comparable T cell responses to ancestral spike, nucleocapsid and membrane proteins to those in patients hospitalized in previous waves dominated by the ancestral, Beta or Delta variants (n = 49). Thus, despite extensive mutations and reduced susceptibility to neutralizing antibodies of Omicron, the majority of T cell responses induced by vaccination or infection cross-recognize the variant. It remains to be determined whether well-preserved T cell immunity to Omicron contributes to protection from severe COVID-19 and is linked to early clinical observations from South Africa and elsewhere^9–12.

Attenuated vaccine strains of lumpy skin disease virus (LSDV) have become increasingly popular as recombinant vaccine vectors, to target both LSDV, as well as other pathogens, including human infectious agents. Historically, these vaccine strains and recombinants were generated in primary (lamb) testis (LT) cells, Madin–Darby bovine kidney (MDBK) cells or in eggs. Growth in eggs is a laborious process, the use of primary cells has the potential to introduce pathogens and MDBK cells are known to harbor bovine viral diarrhea virus (BVDV). In this study, data is presented to show the growth of an attenuated LSDV strain in baby hamster kidney (BHK-21) cells. Subsequently, a recombinant LSDV vaccine was generated in BHK-21 cells. Partial growth was also observed in rabbit kidney cells (RK13), but only when the vaccinia virus host range gene K1L was expressed. Despite the limited growth, the expression of K1L was enough to serve as a positive selection marker for the generation of recombinant LSDV vaccines in RK13 cells. The simplification of generating (recombinant) LSDV vaccines shown here should increase the interest for this platform for future livestock vaccine development and, with BHK-21 cells approved for current good manufacturing practice, this can be expanded to human vaccines as well.

Dual vaccines (n = 6) against both lumpy skin disease (LSD) and bovine ephemeral fever (BEF) were constructed, based on the BEFV glycoprotein (G) gene, with or without the BEFV matrix (M) protein gene, inserted into one of two different LSDV backbones, nLSDV∆SOD-UCT or nLSDVSODis-UCT. The inserted gene cassettes were confirmed by PCR; and BEFV protein was shown to be expressed by immunofluorescence. The candidate dual vaccines were initially tested in a rabbit model; neutralization assays using the South African BEFV vaccine (B-Phemeral) strain showed an African consensus G protein gene (Gb) to give superior neutralization compared to the Australian (Ga) gene. The two LSDV backbones expressing both Gb and M BEFV genes were tested in cattle and shown to elicit neutralizing responses to LSDV as well as BEFV after two inoculations 4 weeks apart. The vaccines were safe in cattle and all vaccinated animals were protected against virulent LSDV challenge, unlike a group of control naïve animals, which developed clinical LSD. Both neutralizing and T cell responses to LSDV were stimulated upon challenge. After two inoculations, all vaccinated animals produced BEFV neutralizing antibodies ≥ 1/20, which is considered protective for BEF.

Bovine leukaemia virus (BLV) causes chronic lymphoproliferative disorder and fatal lymphosarcoma in cattle, leading to significant economic losses in the beef and dairy industries. BLV is endemic globally and eleven genotypes have been identified. To date, only Zambian isolates have been genotyped from Africa. Although high BLV prevalence has been reported in South Africa, there has been no molecular characterisation of South African BLV isolates. To characterise BLV isolates in South Africa for the first time, we investigated the phylogenetic relationships and compared the genetic variability of eight South African BLV isolates with BLV isolates representing the eleven known genotypes from different geographical regions worldwide. Phylogenetic analyses based on full-length and partial env sequences as well as full-length gag sequences revealed that at least two genotypes, genotypes 1 (G1) and 4 (G4), are present in cattle in South Africa, which is consistent with studies from Zambia. However, our analysis revealed that the G1 South African isolate is more similar to other G1 isolates than the G1 Zambian isolates whereas, the G4 South African isolates are more divergent from other G4 isolates but closely related to the G4 Zambian isolate. Lastly, amino acid sequence alignment identified genotype-specific as well as novel amino acid substitutions in the South African isolates. The detection of two genotypes (G1 and G4) in southern Africa highlights the urgent need for disease management and the development of an efficacious vaccine against local strains.

The aim of this study was to characterize HLA diversity in individuals from clinical research sites in order to better understand T cell responses to COVID-19 vaccines in relation to their HLA profiles. Next-generation sequence-based typing of the HLA-A, -B, -C, -DPB1, -DQB1 and -DRB1 loci is reported for 226 individuals from three metropolitan areas in South Africa. Overall, the frequencies of both class I and class II HLA alleles in this study were comparable to those identified in other South African studies. While a more uniform allele frequency prevalence was noted for HLA class I and HLA-DRB1 genes, an allele bias was noted within our population for HLA-DPB1 and -DQB1 alleles, where three most prevalent alleles accounted for allele frequencies of between 12.3 and 29.8%. Our HLA genotyping data will contribute to an expanding catalogue of HLA data from Africa, which are available in the Allele Frequencies Net Database under identifiers 3826, 3827 and 3828.