ABSTRACT
Background Vaccines play a crucial role in eradicating and containing disease outbreaks. Therefore, understanding the reasons behind vaccine refusal and associated factors is essential for improving vaccine acceptance rates. Our objective was to examine the determinants of COVID-19 vaccine non-uptake and explore the reasons for non-uptake among healthcare workers in Uganda. Methods Between July and August 2021, we conducted a cross-sectional study among healthcare workers in primary healthcare facilities in Entebbe Municipality, Uganda. Participants were recruited using convenience sampling, and consenting individuals received credentials to access an electronic database and complete a structured questionnaire. Survey questions were based on the '3Cs' model of vaccine hesitancy, focusing on confidence, convenience, and complacency factors. We employed counts, percentages, and simple logit models to summarize the reasons for non-uptakeof COVID-19 vaccines and to identify associated factors. Results The study recruited 360 healthcare workers, 61.7% of whom were female, with an average age of 31 years (SD=7.9). Among them, 124 (34.4%) healthcare workers did not receive any COVID-19 vaccine. Non-uptake of COVID-19 vaccines was independently associated with several factors, including age [35+ years adjusted odds ratio (aOR)=0.30, 95% CI: 0.13-0.66 compared with 18-24 years], facility ownership [government, aOR=0.22 (0.10-0.49) compared with private not-for-profit], previous testing for coronavirus [yes, aOR=0.35 (0.19-0.65)], and previous involvement in COVID-19 vaccine activities [yes, aOR=0.17 (0.10-0.29)]. The primary reasons cited for non-uptake of COVID-19 vaccines were related to a lack of confidence in the vaccines, such as concerns about side effects (79.8%) and the need for more time to understand the vaccines (89.5%), as well as the importance of weighing benefits and risks (84.7%) before being vaccinated. A smaller proportion, approximately 23%, cited reasons related to complacency and lack of convenience in accessing vaccination services. Conclusion The high proportion of non-uptake of COVID-19 vaccines among this population primarily stems from a lack of confidence and trust in the vaccines, coupled with insufficient time allowed for users to make informed decisions. This underscores the urgent need for ongoing monitoring and trend analysis of vaccine non-uptake to guide the development and implementation of strategies aimed at building and sustaining vaccine confidence.
Subject(s)
COVID-19ABSTRACT
The rapid evolution of SARS-CoV-2 to variants with improved transmission efficiency and reduced sensitivity to vaccine-induced humoral immunity has abolished the protective effect of licensed therapeutic human monoclonal antibodies (mAbs). To fill this unmet medical need and protect vulnerable patient populations, we isolated the P4J15 mAb from a previously infected, vaccinated donor, with <20 ng/ml neutralizing activity against all Omicron variants including the latest XBB.2.3 and EG.1 sub-lineages. Structural studies of P4J15 in complex with Omicron XBB.1 Spike show that the P4J15 epitope shares ~93% of its buried surface area with the ACE2 contact region, consistent with an ACE2 mimetic antibody. Although SARS-CoV-2 mutants escaping neutralization by P4J15 were selected in vitro, these displayed lower infectivity, poor binding to ACE2, and the corresponding "escape" mutations are accordingly rare in public sequence databases. Using a SARS-CoV-2 XBB.1.5 monkey challenge model, we show that P4J15 confers complete prophylactic protection. We conclude that the P4J15 mAb has potential as a broad-spectrum anti-SARS-CoV-2 drug.
ABSTRACT
Background: Routine vaccination is an essential highly successfully public health intervention in the prevention of infectious diseases that greatly depends on high coverage, and health care workers (HCWs) who play a pivotal role in ensuring the high uptake of vaccines in the population. COVID-19 vaccines have been proven efficacious, and vaccination campaigns have been ongoing, however, there is a perceived high vaccine hesitancy among health care workers in Uganda. This study describes the level and determinants of uptake of COVID-19 vaccines among HCWs in Entebbe municipality, Uganda. Materials and methods: We conducted a health facility based cross-sectional study among HCWs from private and government health facilities in Entebbe municipality between July 2021 and August 2021. Structured questionnaires were used, and data were analysed using Stata version 12. We defined uptake as having received at least the first doze of COVID 19 vaccine or completed the two dozes. Results: The level of vaccine uptake was 65.6%with higher uptake among males than females. HCWs aged 30-39 years were 2.7 times more likely to have been vaccinated than those less than 30 years (OR 2.72, 95% CI: 1.26-5.88, P-value <0.01), and the odds of having been vaccinated were 4 times higher among health workers above 40 years (OR 4.29, 95% CI 1.50-12.24, P-value < 0.01). Additionally, the odds of having been vaccinated were 4 times higher among health care workers that participated in COVID-19 vaccine related activities (OR 4.18, 95% CI 2.16-8.10, p-value <0.001). Healthcare workers (98%) had confidence in the vaccines although 45% of those that were not vaccinated felt that the vaccines were ineffective. Conclusion. Vaccine uptake among HCWs was relatively high compared to the WHO recommended uptake of 70% by mid-2022, although some HCWs were still hesitant. The convenience of vaccination services was an important factor in vaccine uptake. Hence, governments should endeavour to improve access to vaccination both for HCWs and the public.
Subject(s)
COVID-19ABSTRACT
The SARS-CoV-2 Omicron variant exhibits very high levels of transmission, pronounced resistance to authorized therapeutic human monoclonal antibodies and reduced sensitivity to vaccine-induced immunity. Here we describe P2G3, a human monoclonal antibody (mAb) isolated from a previously infected and vaccinated donor, which displays picomolar-range neutralizing activity against Omicron BA.1, BA.1.1, BA.2 and all other current variants, and is thus markedly more potent than all authorized or clinically advanced anti-SARS-CoV-2 mAbs. Structural characterization of P2G3 Fab in complex with the Omicron Spike demonstrates unique binding properties to both down and up spike trimer conformations at an epitope that partially overlaps with the receptor-binding domain (RBD), yet is distinct from those bound by all other characterized mAbs. This distinct epitope and angle of attack allows P2G3 to overcome all the Omicron mutations abolishing or impairing neutralization by other anti-SARS-COV-2 mAbs, and P2G3 accordingly confers complete prophylactic protection in the SARS-CoV-2 Omicron monkey challenge model. Finally, although we could isolate in vitro SARS-CoV2 mutants escaping neutralization by P2G3 or by P5C3, a previously described broadly active Class 1 mAb, we found these viruses to be lowly infectious and their key mutations extremely rare in the wild, and we could demonstrate that P2G3/P5C3 efficiently cross-neutralized one another's escapees. We conclude that this combination of mAbs has great prospects in both the prophylactic and therapeutic settings to protect from Omicron and other VOCs.
ABSTRACT
Control of the ongoing SARS-CoV-2 pandemic is endangered by the emergence of viral variants with increased transmission efficiency, resistance to marketed therapeutic antibodies and reduced sensitivity to vaccine-induced immunity. Here, we screened B cells from COVID-19 donors and identified P5C3, a highly potent and broadly neutralizing monoclonal antibody with picomolar neutralizing activity against all SARS-CoV-2 variants of concern (VOC) identified to date. Structural characterization of P5C3 Fab in complex with the Spike demonstrates a neutralizing activity defined by a large buried surface area, highly overlapping with the receptor-binding domain (RBD) surface necessary for ACE2 interaction. We further demonstrate that P5C3 showed complete prophylactic protection in the SARS-CoV-2 infected hamster challenge model. These results indicate that P5C3 opens exciting perspectives either as a prophylactic agent in immunocompromised individuals with poor response to vaccination or as combination therapy in SARS-CoV-2-infected individuals.Funding: This CARE project has received funding from the Innovative MedicinesInitiative 2 Joint Undertaking (JU) under grant agreement No 101005077. The JU receives support from the European Union’s Horizon 2020 research and innovation program and EFPIA and BILL & MELINDA GATES FOUNDATION, GLOBAL HEALTH DRUG DISCOVERYINSTITUTE, UNIVERSITY OF DUNDEE. Furthermore, funding was also provided through the Lausanne University Hospital, through the Swiss Vaccine Research Institute to G.P., and through the EPFL COVID fund to D.T.Conflict of Interest: None to declare. Ethical Approval: Study design and use of subject samples were approved by the Institutional Review Board of the Lausanne University Hospital and the ‘Commission d’éthique du Canton de Vaud’ (CER-VD).