SARS-CoV-2 vaccines in advanced clinical trials: Where do we stand?

Chakraborty, Saborni; Mallajosyula, Vamsee; Tato, Cristina M.; Tan, Gene S.; Wang, Taia T.

doi:10.1016/j.addr.2021.01.014

Cited by 81 publications

(72 citation statements)

References 278 publications

(249 reference statements)

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“…The seroconversion rate of 97% for the anti-S1 IgG observed in HCWs is important data for the scientific community, since in phase III studies of this and other vaccine candidates for SARS-CoV-2, similar or lower seroconversion rates were observed 9 .…”

Section: Discussionmentioning

confidence: 95%

Dynamic of humoral response to SARS-CoV-2 anti Nucleocapsid and Spike proteins after CoronaVac vaccination

Bochnia-Bueno

SMd

et al. 2021

Preprint

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Background: This study aimed to calculate the seroconversion rate of the CoronaVac vaccine in healthcare workers (HCWs) 40 days after administration. Methods: Serum samples from 133 HCWs from Southern Brazil were collected one day before (Day 0) and 10, 20, and 40 days after administering the vaccines first dose. Immunoglobulin G (IgG) was quantified using immunoassays for anti-N-protein antibodies (Abbott, Sligo, Ireland) and for anti-S1 (spike) protein antibodies (Euroimmun, Lubeck, Germany). Results: Seroconversion by D 40 (20 days after the second dose) occurred in 129 (97%) HCWs for the S1 protein, and in 69 (51.87%) HCWs for the N protein. An absence of IgG antibodies (by both methodologies), occurred in two (1.5%) HCWs undergoing semiannual rituximab administration, and also in another two (1.5%) HCWs with no apparent reason. Conclusion: This study showed that CoronaVac has a high seroconversion rate when evaluated in an HCW population.

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Section: Discussionmentioning

confidence: 95%

Dynamic of humoral response to SARS-CoV-2 anti Nucleocapsid and Spike proteins after CoronaVac vaccination

Bochnia-Bueno

SMd

et al. 2021

Preprint

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“…A phase 3 study is currently underway in Abu Dhabi with 15,000 participants: 5000 participants receiving placebo, another 5000 receiving BBIBP-CorV, and the remaining 5000 receiving another inactivated vaccine manufacturer by Sinopharm [ 23 ].…”

Section: Bbibp-corvmentioning

confidence: 99%

COVID-19 Vaccines: A Review of the Safety and Efficacy of Current Clinical Trials

2021

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Various strategies have been designed to contain the COVID-19 pandemic. Among them, vaccine development is high on the agenda in spite of the unknown duration of the protection time. Various vaccines have been under clinical trials with promising results in different countries. The protective efficacy and the short-term and long-term side effects of the vaccines are of major concern. Therefore, comparing the protective efficacy and risks of vaccination is essential for the global control of COVID-19 through herd immunity. This study reviews the most recent data of 12 vaccines to evaluate their efficacy, safety profile and usage in various populations.

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“…According to the reports of the World Health Organization (WHO), SARS-CoV-2 has led to 93,194,922 infection cases and 2,014,729 deaths until 17 January 2021 [1], which poses great threats to public health and brings heavy burdens to global economy. The significant progress in the developments of COVID-19 vaccines [2,3], including inactivated vaccine [4], mRNA vaccine [5,6], live vectorial vaccine [7,8] and recombinant protein subunit vaccine [9,10], as well as the neutralizing antibody therapeutics [11,12] is encouraging to prevent the pandemic of SARS-CoV-2. However, the virus is in constant evolution and several more contagious variants have emerged [13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

E484K mutation in SARS-CoV-2 RBD enhances binding affinity with hACE2 but reduces interactions with neutralizing antibodies and nanobodies: Binding free energy calculation studies

Wang

Liang

Jin

et al. 2021

Preprint

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The pandemic of the COVID-19 disease caused by SARS-CoV-2 has led to more than 100 million infections and over 2 million deaths worldwide. The progress in the developments of effective vaccines and neutralizing antibody therapeutics brings hopes to eliminate the threat of COVID-19. However, SARS-CoV-2 continues to mutate, and several new variants have been emerged. Among the various naturally-occurring mutations, the E484K mutation shared by both the 501Y.V2 and 501Y.V3 variants attracted serious concerns, which may potentially enhance the receptor binding affinity and reduce the immune response. In the present study, the molecular mechanism behind the impacts of E484K mutation on the binding affinity of the receptor-binding domain (RBD) with the receptor human angiotensin-converting enzyme 2 (hACE2) was investigated by using the molecular dynamics (MD) simulations combined with the molecular mechanics-generalized Born surface area (MMGBSA) method. Our results indicate that the E484K mutation results in more favorable electrostatic interactions compensating the burial of the charged and polar groups upon the binding of RBD with hACE2, which significantly improves the RBD-hACE2 binding affinity. Besides that, the E484K mutation also causes the conformational rearrangements of the loop region containing the mutant residue, which leads to more tight binding interface of RBD with hACE2 and formation of some new hydrogen bonds. The more tight binding interface and the new hydrogen bonds formation also contribute to the improved binding affinity of RBD to the receptor hACE2. In addition, six neutralizing antibodies and nanobodies complexed with RBD were selected to explore the effects of E484K mutation on the recognition of these antibodies to RBD. The simulation results show that the E484K mutation significantly reduces the binding affinities to RBD for most of the studied neutralizing antibodies, and the decrease in the binding affinities is mainly owing to the unfavorable electrostatic interactions caused by the mutation. Our studies revealed that the E484K mutation may improve the binding affinity between RBD and the receptor hACE2, implying more transmissibility of the E484K-containing variants, and weaken the binding affinities between RBD and the studied neutralizing antibodies, indicating reduced effectiveness of these antibodies. Our results provide valuable information for the effective vaccine development and antibody drugs design.

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SARS-CoV-2 vaccines in advanced clinical trials: Where do we stand?

Cited by 81 publications

References 278 publications

Dynamic of humoral response to SARS-CoV-2 anti Nucleocapsid and Spike proteins after CoronaVac vaccination

Dynamic of humoral response to SARS-CoV-2 anti Nucleocapsid and Spike proteins after CoronaVac vaccination

COVID-19 Vaccines: A Review of the Safety and Efficacy of Current Clinical Trials

E484K mutation in SARS-CoV-2 RBD enhances binding affinity with hACE2 but reduces interactions with neutralizing antibodies and nanobodies: Binding free energy calculation studies

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