(1) Background: By October 2022, vaccination rates with at least one dose of a COVID-19 vaccine were low among adolescent girls aged 12–17 (38%) and young women aged 18–34 (45%) in South Africa. This study aimed to measure and identify barriers to and facilitators of motivation to take up, access to, and uptake of COVID-19 vaccines among schoolgoing adolescent girls and young women in two districts in South Africa. (2) Methods: Using the theory of the HIV prevention cascade, we conceptualised the relationship between motivation, access, and uptake of COVID-19 vaccines, and associated barriers. Potential barriers and facilitators were identified using bivariate and multivariable Poisson regression. (3) Results: Among all 2375 participants, access was high (69%), but motivation (49%) and vaccination with at least one COVID-19 vaccine (45%) were lower. Fear of injections was a barrier to vaccine uptake (aRR 0.85 95% CI 0.82–0.88), while being tested for COVID-19 (aRR 2.10 95% CI 1.85–2.38) and believing that the COVID-19 vaccine was safe (aRR 1.31 95% CI 1.18–1.44) and would prevent you from getting very sick (aRR 1.11 95% CI 1.04–1.19) were facilitators. (4) Conclusions: The controversy about the value of vaccinating adolescents and the delay in vaccine rollout for adolescents and young adults may have contributed to fears about the safety and efficacy of COVID-19 vaccines, as well as a lack of motivation to get vaccinated.

Background: As mortality declined significantly during the fourth and fifth waves compared to previous waves, the question of the future role of COVID-19 vaccination arose among both experts and the public in South Africa. Turning attention away from the general public, now considered to be at very low risk of severe COVID-19 disease, a commonly held view was that the vaccination campaign should focus only on those who remain highly vulnerable to severe disease and death from COVID-19. Primary amongst this group are patients with common chronic diseases attending hospital outpatient departments. We hypothesized that providing COVID-19 vaccinations on-site at a central hospital will increase uptake for the patients with co-morbid chronic conditions who need them most in the Omicron phase of the pandemic. Aim: Evaluate the acceptability, need, and uptake of a hospital-based vaccination site for patients attending the medical hospital outpatient departments. Objectives: To assess vaccination uptake, coverage, and hesitancy in people attending a central hospital, to determine factors associated with and influencing vaccination uptake, and to document implementation and assess acceptability of the vaccination project among staff and persons attending the hospital. Methods: Mixed-methods study using quantitative and qualitative methods. Results: Of the 317 participants enrolled in the study, 229 (72%) had already received at least one dose of the COVID-19 vaccine. A total of 296 participants were eligible for a first vaccination, additional vaccination, or booster vaccination according to the South African Department of Health guidelines. Of those previously vaccinated, 65% opted for an additional dose on the day it was offered (same day). Only 13 previously unvaccinated participants (15% of vaccine naïve participants) opted for vaccination, increasing vaccine coverage with at least one dose from 72% to 76%. Approximately 24% (n = 75) of all participants refused vaccination (vaccine hesitant). Variables tested for an association with vaccination status demonstrated that age reached statistical significance. Emerging themes in the qualitative analysis included perceptions of vulnerability, vaccine safety and efficacy concerns, information gaps regarding vaccinations, the value of convenience in the decision to vaccinate, and the role of health promoters. Conclusions: This study has shown that it is logistically acceptable to provide a vaccination site at a large hospital targeting patients attending outpatient services for chronic medical conditions. This service also benefits accompanying persons and hospital staff. Access and convenience of the vaccination site influence decision-making, increasing the opportunity to vaccinate. However, vaccine hesitancy is widespread with just under one-quarter of all those offered vaccinations remaining unvaccinated. Strengthening health education and patient–clinician engagement about the benefits of vaccination is essential to reach highly vulnerable populations routinely attending hospital outpatient departments with an appropriate vaccination program.

People living with HIV (PLWH) who experience advanced immunosuppression are susceptible to severe COVID-19 and demonstrate compromised vaccine responses due to low CD4 counts and uncontrolled HIV viral load. Although vaccine boosters enhance immunity in the general population, their immunogenicity in individuals with advanced HIV remains inadequately characterised. This study evaluated the humoral and cellular immunogenicity of COVID-19 vaccine boosters in 41 individuals with advanced HIV at baseline and 4 weeks post-vaccination. Binding antibodies, neutralising antibodies, antibody-dependent cellular cytotoxicity (ADCC), as well as spike-specific CD4+ and CD8+ T-cell responses were quantified and characterised. Booster vaccination was found to increase binding antibody titres (8.0-fold) and neutralising activity (3.9-fold), even among participants with CD4 counts <100 cells/mm³, although absolute responses remained lower than the controls. ADCC activity also modestly increased post-vaccination (2.1-fold). Spike-specific CD4+ T-cell responses increased in magnitude (0.001% to 0.160%, p=0.0001) and responder frequency (49% to 83%, p=0.0167) post-vaccination, while CD8+ T-cell responses remained low. Compared to the controls, PLWH had similar magnitudes of spike-specific CD4+ T-cell responses but significantly lower CD8+ T-cell responses. COVID-19 vaccine boosters enhance immunity in PLWH, however, the responses remain suboptimal compared to immunocompetent individuals, emphasising the need for tailored vaccination strategies.