An Effective COVID-19 Vaccine Needs to Engage T Cells

Sauer, Karsten; Harris, Tim

doi:10.3389/fimmu.2020.581807

Cited by 82 publications

(75 citation statements)

References 77 publications

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“…20 This study has some further limitations. First, although much evidence supports the important role of a T cell response to COVID-19, 27 and such responses have been observed with use of mRNA vaccines and adenoviralvectored vaccines, [9][10][11][12]28,29 those tests were not done in this study. However, we detected IFN-γ as an indicator of T-cell responses following vaccination in our phase 1 trial among adults aged 18-59 years, and the results showed that the responses induced by CoronaVac were low.…”

Section: Discussionmentioning

confidence: 80%

Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine (CoronaVac) in healthy adults aged 60 years and older: a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial

et al. 2021

The Lancet Infectious Diseases

514

482

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Background A vaccine against COVID-19 is urgently needed for older adults, in whom morbidity and mortality due to the disease are increased. We aimed to assess the safety, tolerability, and immunogenicity of a candidate COVID-19 vaccine, CoronaVac, containing inactivated SARS-CoV-2, in adults aged 60 years and older. Methods We did a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial of CoronaVac in healthy adults aged 60 years and older in Renqiu (Hebei, China). Vaccine or placebo was given by intramuscular injection in two doses (days 0 and 28). Phase 1 comprised a dose-escalation study, in which participants were allocated to two blocks: block 1 (3 μg inactivated virus in 0•5 mL of aluminium hydroxide solution per injection) and block 2 (6 μg per injection). Within each block, participants were randomly assigned (2:1) using block randomisation to receive CoronaVac or placebo (aluminium hydroxide solution only). In phase 2, participants were randomly assigned (2:2:2:1) using block randomisation to receive either CoronaVac at 1•5 μg, 3 µg, or 6 µg per dose, or placebo. All participants, investigators, and laboratory staff were masked to treatment allocation. The primary safety endpoint was adverse reactions within 28 days after each injection in all participants who received at least one dose. The primary immunogenicity endpoint was seroconversion rate at 28 days after the second injection (which was assessed in all participants who had received the two doses of vaccine according to their random assignment, had antibody results available, and did not violate the trial protocol). Seroconversion was defined as a change from seronegative at baseline to seropositive for neutralising antibodies to live SARS-CoV-2 (positive cutoff titre 1/8), or a four-fold titre increase if the participant was seropositive at baseline. This study is ongoing and is registered with ClinicalTrials.gov (NCT04383574). Findings Between May 22 and June 1, 2020, 72 participants (24 in each intervention group and 24 in the placebo group; mean age 65•8 years [SD 4•8]) were enrolled in phase 1, and between June 12 and June 15, 2020, 350 participants were enrolled in phase 2 (100 in each intervention group and 50 in the placebo group; mean age 66•6 years [SD 4•7] in 349 participants). In the safety populations from both phases, any adverse reaction within 28 days after injection occurred in 20 (20%) of 100 participants in the 1•5 μg group, 25 (20%) of 125 in the 3 μg group, 27 (22%) of 123 in the 6 μg group, and 15 (21%) of 73 in the placebo group. All adverse reactions were mild or moderate in severity and injection site pain (39 [9%] of 421 participants) was the most frequently reported event. As of Aug 28, 2020, eight serious adverse events, considered unrelated to vaccination, have been reported by seven (2%) participants. In phase 1, seroconversion after the second dose was observed in 24 of 24 participants (100•0% [95% CI 85•8-100•0]) in the 3 μg group and 22 of 23 (95•7% [78•1-99•9]) in the 6 μg group. In phase 2, sero...

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Section: Discussionmentioning

confidence: 80%

Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine (CoronaVac) in healthy adults aged 60 years and older: a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial

et al. 2021

The Lancet Infectious Diseases

514

482

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“…If not controlled by the immune response, it can evolve into a lethal pneumonia with immunopathology due to excessive amplification of the innate inflammatory response, complicated by several extra-respiratory manifestations ( 1 ). While humoral responses play an important role in immunological control of infection, the generation of effective cellular immunity and expansion of cytotoxic CD8 + memory T cells is also required to eliminate virally infected cells as shown from the earlier SARS-CoV-1 epidemic, even in the absence of seroconversion ( 2-7 ).…”

Section: Introductionmentioning

confidence: 99%

Allelic variation in Class I HLA determines pre-existing memory responses to SARS-CoV-2 that shape the CD8⁺ T cell repertoire upon viral exposure

Francis¹,

Leistritz-Edwards²,

Dunn³

et al. 2021

Preprint

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Effective presentation of antigens by HLA class I molecules to CD8+ T cells is required for viral elimination and generation of long-term immunological memory. In this study, we applied a single-cell, multi-omic technology to generate the first unified ex vivo characterization of the CD8+ T cell response to SARS-CoV-2 across 4 major HLA class I alleles. We found that HLA genotype conditions key features of epitope specificity, TCR a/b sequence diversity, and the utilization of pre-existing SARS-CoV-2 reactive memory T cell pools. Single-cell transcriptomics revealed functionally diverse T cell phenotypes of SARS-CoV-2-reactive T cells, associated with both disease stage and epitope specificity. Our results show that HLA variations influence pre-existing immunity to SARS-CoV-2 and shape the immune repertoire upon subsequent viral exposure.

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“…In particular, pathogen–host interaction is a complex process where the pathogen is processed by the pattern recognition receptors and presented by antigen-presenting cells to T and B-cells to elicit an effective immune response [ 6 , 7 ]. The immune response as evaluated by detectable IgG antibody levels and cytotoxic T-cell activity depends on the antigen that cancause varying symptoms ranging from mild fever to lethality [ 8 , 9 , 10 ]. Such an immune response elicited towards the virus is affected by several factors such as the evolution of the virus, ethnicity, and geography [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Comparison of Immunological Profiles of SARS-CoV-2 Variants in the COVID-19 Pandemic Trends: An Immunoinformatics Approach

Ambrose¹,

Veeraraghavan

Kullappan³

et al. 2021

Antibiotics

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The current dynamics of the COVID-19 pandemic have become a serious concern with the emergence of a series of mutant variants of the SARS-CoV-2 virus. Unlike the previous strain, it is reported that the descendants are associated with increased risk of transmission yet causing less impact in terms of hospital admission, the severity of illness, or mortality. Moreover, the vaccine efficacy is also not believed to vary among the population depending on the variants of the virus and ethnicity. It has been determined that the mutations recorded in the spike gene and protein of the newly evolved viruses are specificallyresponsible for this transformation in the behavior of the virus and its disease condition. Hence, this study aimed to compare the immunogenic profiles of the spike protein from the latest variants of the SARS-CoV-2 virus concerning the probability of COVID-19 severity. Genome sequences of the latest SARS-CoV-2 variants were obtained from GISAID and NCBI repositories. The translated protein sequences were run against T-cell and B-cell epitope prediction tools. Subsequently, antigenicity, immunogenicity, allergenicity, toxicity, and conservancy of the identified epitopes were ascertained using various prediction servers. Only the non-allergic and non-toxic potential epitopes were matched for population relevance by using the Human Leucocyte Antigen population registry in IEDB. Finally, the selected epitopes were validated by docking and simulation studies. The evaluated immunological parameters would concurrently reveal the severity of COVID-19, determining the infection rate of the pathogen. Our immunoinformatics approach disclosed that spike protein of the five variants was capable of forming potential T and B-cell epitopes with varying immune responses. Although the Wuhan strain showed a high number of epitope/HLA combinations, relatively less antigenicity and higher immunogenicity results in poor neutralizing capacity, which could be associated with increased disease severity. Our data demonstrate that increased viral antigenicity with moderate to high immunogenicity, and several potential epitope/HLA combinations in England strain, the USA, India, and South Africa variants,could possess a high neutralizing ability. Therefore, our findings reinforce that the newly circulating variants of SARS-CoV-2 might be associated with more infectiousness and less severe disease condition despite their greater viremia, as reported in the recent COVID-19 cases, whichconsequently determine their increased epidemiological fitness.

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An Effective COVID-19 Vaccine Needs to Engage T Cells

Cited by 82 publications

References 77 publications

Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine (CoronaVac) in healthy adults aged 60 years and older: a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial

Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine (CoronaVac) in healthy adults aged 60 years and older: a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial

Allelic variation in Class I HLA determines pre-existing memory responses to SARS-CoV-2 that shape the CD8⁺ T cell repertoire upon viral exposure

Comparison of Immunological Profiles of SARS-CoV-2 Variants in the COVID-19 Pandemic Trends: An Immunoinformatics Approach

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An Effective COVID-19 Vaccine Needs to Engage T Cells

Cited by 82 publications

References 77 publications

Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine (CoronaVac) in healthy adults aged 60 years and older: a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial

Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine (CoronaVac) in healthy adults aged 60 years and older: a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial

Allelic variation in Class I HLA determines pre-existing memory responses to SARS-CoV-2 that shape the CD8+ T cell repertoire upon viral exposure

Comparison of Immunological Profiles of SARS-CoV-2 Variants in the COVID-19 Pandemic Trends: An Immunoinformatics Approach

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Allelic variation in Class I HLA determines pre-existing memory responses to SARS-CoV-2 that shape the CD8⁺ T cell repertoire upon viral exposure