The COVID-19 pandemic has had widespread effects across the globe, and its causative agent, SARS-CoV-2, continues to spread. Effective interventions need to be developed to end this pandemic. Single ...and combination therapies with monoclonal antibodies have received emergency use authorization
, and more treatments are under development
. Furthermore, multiple vaccine constructs have shown promise
, including two that have an approximately 95% protective efficacy against COVID-19
. However, these interventions were directed against the initial SARS-CoV-2 virus that emerged in 2019. The recent detection of SARS-CoV-2 variants B.1.1.7 in the UK
and B.1.351 in South Africa
is of concern because of their purported ease of transmission and extensive mutations in the spike protein. Here we show that B.1.1.7 is refractory to neutralization by most monoclonal antibodies against the N-terminal domain of the spike protein and is relatively resistant to a few monoclonal antibodies against the receptor-binding domain. It is not more resistant to plasma from individuals who have recovered from COVID-19 or sera from individuals who have been vaccinated against SARS-CoV-2. The B.1.351 variant is not only refractory to neutralization by most monoclonal antibodies against the N-terminal domain but also by multiple individual monoclonal antibodies against the receptor-binding motif of the receptor-binding domain, which is mostly due to a mutation causing an E484K substitution. Moreover, compared to wild-type SARS-CoV-2, B.1.351 is markedly more resistant to neutralization by convalescent plasma (9.4-fold) and sera from individuals who have been vaccinated (10.3-12.4-fold). B.1.351 and emergent variants
with similar mutations in the spike protein present new challenges for monoclonal antibody therapies and threaten the protective efficacy of current vaccines.
The entire world has been suffering from the coronavirus disease 2019 (COVID‐19) pandemic since March 11, 2020. More than a year later, the COVID‐19 vaccination brought hope to control this viral ...pandemic. Here, we review the unknowns of the COVID‐19 vaccination, such as its longevity, asymptomatic spread, long‐term side effects, and its efficacy on immunocompromised patients. In addition, we discuss challenges associated with the COVID‐19 vaccination, such as the global access and distribution of vaccine doses, adherence to hygiene guidelines after vaccination, the emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) variants, and vaccine resistance. Despite all these challenges and the fact that the end of the COVID‐19 pandemic is still unclear, vaccines have brought great hope for the world, with several reports indicating a significant decline in the risk of COVID19‐related infection and hospitalizations.
Highlights
1.
Vaccination plays a pivotal role in reducing the death toll of the COVID‐19 infection.
2.
The immunity provided by vaccines is still disputable leading to some challenges like the asymptomatic spread; therefore, staying strict to hygiene guidelines is necessary.
3.
Hence, COVID‐19 vaccines' related long‐term side effects are still unknown; cautions should be taken when injected to various individuals of the community.
4.
COVID‐19 vaccines' effectiveness are strongly related to their effect on emergent COVID‐19 variants, but until now approved vaccines can still show some protective effects against new variants.
The global supply of COVID-19 vaccines remains limited. An understanding of the immune response that is predictive of protection could facilitate rapid licensure of new vaccines. Data from a ...randomized efficacy trial of the ChAdOx1 nCoV-19 (AZD1222) vaccine in the United Kingdom was analyzed to determine the antibody levels associated with protection against SARS-CoV-2. Binding and neutralizing antibodies at 28 days after the second dose were measured in infected and noninfected vaccine recipients. Higher levels of all immune markers were correlated with a reduced risk of symptomatic infection. A vaccine efficacy of 80% against symptomatic infection with majority Alpha (B.1.1.7) variant of SARS-CoV-2 was achieved with 264 (95% CI: 108, 806) binding antibody units (BAU)/ml: and 506 (95% CI: 135, not computed (beyond data range) (NC)) BAU/ml for anti-spike and anti-RBD antibodies, and 26 (95% CI: NC, NC) international unit (IU)/ml and 247 (95% CI: 101, NC) normalized neutralization titers (NF
) for pseudovirus and live-virus neutralization, respectively. Immune markers were not correlated with asymptomatic infections at the 5% significance level. These data can be used to bridge to new populations using validated assays, and allow extrapolation of efficacy estimates to new COVID-19 vaccines.
Haematology and biochemistry safety monitoring blood results are also reported from the immunology cohort (100 participants with additional visits), at baseline (before the prime dose), at day 28 ...(before the boost dose) and 7 days post-boost, graded according to a modified US Food and Drug Administration toxicity scale (appendix). In this interim safety analysis, we found an increase in systemic reactogenicity after the boost dose reported by participants in heterologous vaccine schedules in comparison to homologous vaccine schedules, and this was accompanied by increased paracetamol usage. Of note, these data were obtained in participants aged 50 years and older, and reactogenicity might be higher in younger age groups4,5 for whom a mixed vaccination schedule is being advocated in Germany, France, Sweden, Norway, and Denmark among those who have received a ChAd prime dose, in light of concerns regarding thrombotic thrombocytopenia after the first dose of ChAd.6 Pending availability of a more complete safety dataset and immunogenicity results for heterologous prime-boost schedules (to be reported shortly), these data suggest that the two heterologous vaccine schedules in this trial might have some short-term disadvantages.
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