Structural, Social, and Contextual factors influencing COVID-19 vaccine uptake: A qualitative methods study among Healthcare Workers and Older People in Uganda. (preprint)

Background: The COVID-19 vaccine rollout program in Uganda was launched in March 2021 with Healthcare Workers (HCWs), older persons (50 years and above), and persons with chronic conditions as priority groups for vaccination. To inform the vaccine rollout efforts, we set out to explore the social and structural factors that influenced the uptake of COVID-19 vaccines among HCWs and older people in Uganda. Methods Between September and October 2021, we conducted 33 in-depth interviews with 25 HCWs aged 21 to 63 years from three hospitals from two districts in the central region of Uganda and eight older people from communities in Wakiso district. Selection was purposive based on sex, occupation, education, cadre of HCWs (doctors, nurses, laboratory technologist, hospital support staff, administrator) and vaccination status. We explored participants knowledge, beliefs, personal experiences, barriers, and facilitators to vaccine uptake and suggestions for future COVID-19 vaccine rollout. Interviews were audio-recorded, data was transcribed and translated from the local language, coded, and analysed by themes. Results Twenty-two of the 25 (88%) HCWs and 3 of the 8 (38%) older people had received at least one dose of the COVID-19 vaccine at the time of interview. The structural facilitating factors to vaccine uptake included access to correct information, fear of a risky work environment, and mandatory vaccination requirements especially for frontline HCWs. Old age, chronic health conditions, and the fear of death are contextual facilitating factors, while influence from leaders was the main social facilitating factor. Myths and misconceptions about COVID-19 vaccines and the fear of side effects were common social barriers to vaccine uptake among HCWs and older people. Long distances to vaccination centres, vaccine stock-outs, and long queues at the vaccination centres were specific barriers to vaccine uptake for older people. The prerequisite of signing a consent form was a specific structural barrier for the HCWs. Transport challenges linked to long distances to the vaccination centres, for older people, and having underlying chronic health conditions, for both older people and HCWs, were the reported contextual factors. Conclusion Future roll out of new vaccines should have a comprehensive information dissemination strategy about the vaccines. Improved access to vaccines through community outreaches, reliable vaccine supply and addressing vaccine misinformation, may enhance COVID-19 vaccine uptake in Uganda and other future mass vaccination campaigns.

High-resolution African HLA resource uncoversHLA-DRB1expression effects underlying vaccine response (preprint)

How human genetic variation contributes to vaccine immunogenicity and effectiveness is unclear, particularly in infants from Africa. We undertook genome-wide association analyses of eight vaccine antibody responses in 2,499 infants from three African countries and identified significant associations across the human leukocyte antigen (HLA) locus for five antigens spanning pertussis, diphtheria and hepatitis B vaccines. Using high-resolution HLA typing in 1,706 individuals from 11 African populations we constructed a continental imputation resource to fine-map signals of association across the class II HLA observing genetic variation explaining up to 10% of the observed variance in antibody responses. Using follicular helper T-cell assays, in silico binding, and immune cell eQTL datasets we find evidence of HLA-DRB1 expression correlating with serological response and inferred protection from pertussis following vaccination. This work improves our understanding of molecular mechanisms underlying HLA associations that should support vaccine design and development across Africa with wider global relevance. Teaser High-resolution typing of HLA diversity provides mechanistic insights into differential potency and inferred effectiveness of vaccines across Africa.