SARS-CoV-2–Specific Vaccine Candidates; the Contribution of Structural Vaccinology

Pack, Su Min; Peters, Peter J.

doi:10.3390/vaccines10020236

Cited by 16 publications

(14 citation statements)

References 94 publications

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“…Current vaccines have been shown to induce highly effective CD8 + T cell responses, but generally only exploit the S protein. 51 This means that vaccine‐induced CD8 + T cells target a narrow range of spike‐derived epitopes. The current study identified 10 spike‐derived epitopes across eight HLA‐I allotypes, of which A*02:01/s 269–277 , A*03:01/S 378–386 and A*24:02/S 1208–1216 are the only epitopes that induced high CD8 + T cell frequencies in the majority of convalescent donors expressing the respective HLA‐I allotype.…”

Section: Discussionmentioning

confidence: 99%

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Parallel detection of SARS‐CoV‐2 epitopes reveals dynamic immunodominance profiles of CD8⁺ T memory cells in convalescent COVID‐19 donors

et al. 2022

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Objectives High‐magnitude CD8 + T cell responses are associated with mild COVID‐19 disease; however, the underlying characteristics that define CD8 + T cell‐mediated protection are not well understood. The antigenic breadth and the immunodominance hierarchies of epitope‐specific CD8 + T cells remain largely unexplored and are essential for the development of next‐generation broad‐protective vaccines. This study identified a broad spectrum of conserved SARS‐CoV‐2 CD8 + T cell epitopes and defined their respective immunodominance and phenotypic profiles following SARS‐CoV‐2 infection. Methods CD8 + T cells from 51 convalescent COVID‐19 donors were analysed for their ability to recognise 133 predicted and previously described SARS‐CoV‐2‐derived peptides restricted by 11 common HLA class I allotypes using heterotetramer combinatorial coding, which combined with phenotypic markers allowed in‐depth ex vivo profiling of CD8 + T cell responses at quantitative and phenotypic levels. Results A comprehensive panel of 49 mostly conserved SARS‐CoV‐2‐specific CD8 + T cell epitopes, including five newly identified low‐magnitude epitopes, was established. We confirmed the immunodominance of HLA‐A*01:01/ORF1ab 1637–1646 and B*07:02/N 105–113 and identified B*35:01/N 325–333 as a third epitope with immunodominant features. The magnitude of subdominant epitope responses, including A*03:01/N 361–369 and A*02:01/S 269–277 , depended on the donors' HLA‐I context. All epitopes expressed prevalent memory phenotypes, with the highest memory frequencies in severe COVID‐19 donors. Conclusion SARS‐CoV‐2 infection induces a predominant CD8 + T memory response directed against a broad spectrum of conserved SARS‐CoV‐2 epitopes, which likely contributes to long‐term protection against severe disease. The observed immunodominance hierarchy emphasises the importance of T cell epitopes derived from nonspike proteins to the overall protective and cross‐reactive immune response, which could aid future vaccine strategies.

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Section: Discussionmentioning

confidence: 99%

“…Vaccination is the most effective way to protect against (severe) COVID‐19. Current vaccines have been shown to induce highly effective CD8 + T cell responses, but generally only exploit the S protein 51 . This means that vaccine‐induced CD8 + T cells target a narrow range of spike‐derived epitopes.…”

Section: Discussionmentioning

confidence: 99%

Parallel detection of SARS‐CoV‐2 epitopes reveals dynamic immunodominance profiles of CD8⁺ T memory cells in convalescent COVID‐19 donors

et al. 2022

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“…Beyond the approved anti-COVID-19 front-line vaccines based on expressible embedded mRNA and replicationincompetent adenovirus vectors [118,231,232], a recombinant vaccine has come to market (Table 1, [157]) and other many alternative recombinant vaccines are also approached through under fast developing strategies. Because of the broad clinical experience in protein-based vaccination, such protein-based vaccines are expected to enter the prophylaxis landscape and complement or even substitute, in the longer term, the nucleic acid versions [233][234][235][236]. Due to the enormous investment in testing immunization strategies against SARS-CoV-2 infection, a comprehensive and updated overview of the spectrum of vaccine prototypes is just not feasible and it is beyond the scope of this review.…”

Section: Recombinant Vaccines For Covid-19mentioning

confidence: 99%

Recombinant vaccines in 2022: a perspective from the cell factory

et al. 2022

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The last big outbreaks of Ebola fever in Africa, the thousands of avian influenza outbreaks across Europe, Asia, North America and Africa, the emergence of monkeypox virus in Europe and specially the COVID-19 pandemics have globally stressed the need for efficient, cost-effective vaccines against infectious diseases. Ideally, they should be based on transversal technologies of wide applicability. In this context, and pushed by the above-mentioned epidemiological needs, new and highly sophisticated DNA-or RNA-based vaccination strategies have been recently developed and applied at large-scale. Being very promising and effective, they still need to be assessed regarding the level of conferred long-term protection. Despite these fast-developing approaches, subunit vaccines, based on recombinant proteins obtained by conventional genetic engineering, still show a wide spectrum of interesting potentialities and an important margin for further development. In the 80’s, the first vaccination attempts with recombinant vaccines consisted in single structural proteins from viral pathogens, administered as soluble plain versions. In contrast, more complex formulations of recombinant antigens with particular geometries are progressively generated and explored in an attempt to mimic the multifaceted set of stimuli offered to the immune system by replicating pathogens. The diversity of recombinant antimicrobial vaccines and vaccine prototypes is revised here considering the cell factory types, through relevant examples of prototypes under development as well as already approved products.

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“…The entire S protein (BNT162b2/COMIRNATY Tozinameran (INN) (Pfizer, USA (BNT162b2)); NVX-CoV2373/Covovax/Nuvaxovid/Novavax (Novavax, India (NVX-CoV2373)); MVC-COV1901 (Medigen, Germany (MVC-COV1901)); mRNA-1273/Spikevax (Moderna, USA (mRNA-1273)); and EpiVacCorona (Vector State Research Center of Virology and Biotechnology, Russia)), its receptor-binding domain (RBD) (Abdala, CIGB, Cuba (Abdala)), which is responsible for the binding of the virus to the angiotensin-converting enzyme 2 (ACE) receptor, and the N-terminal domain (NTD) are primarily used in the development of COVID-19 vaccines [ 14 , 15 ].…”

Section: Covid-19 Vaccine Platforms and Their Characteristicsmentioning

confidence: 99%

COVID-19 Vaccines: An Updated Overview of Different Platforms

2022

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Vaccination has been identified as a critical method of disease control in the context of the current COVID-19 pandemic. The goal of this review is to update information on vaccine development and to identify areas of concern that require further research. We reviewed the literature on the development of COVID-19 vaccines, their efficacy, and use in special populations, as well as current vaccination strategies. To date, 170 vaccines are in clinical development, with 41 being already approved for use in various countries. The majority of vaccines approved for human use are vector-, subunit-, DNA-, or mRNA-based vaccines, or inactivated viruses. Because of the ongoing mutation of the SARS-CoV-2 virus, well-studied vector vaccines are losing relevance due to the ability of new virus strains to bypass neutralizing antibodies. Simultaneously, PS-based vaccines are becoming more popular. There is mounting evidence that the immunogenicity of COVID-19 vaccines is linked to their clinical efficacy. This has resulted in a shift in vaccination strategies, as well as the use of booster doses and revaccination. Furthermore, vaccination restrictions for children, pregnant women, the elderly, and people with chronic immunosuppressive diseases have been lifted, allowing more people to be vaccinated. New data on vaccine safety, including the incidence of serious adverse events, have been collected. Despite significant advances in the development of and research on COVID-19 vaccines, many questions remain that require further investigation.

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SARS-CoV-2–Specific Vaccine Candidates; the Contribution of Structural Vaccinology

Cited by 16 publications

References 94 publications

Parallel detection of SARS‐CoV‐2 epitopes reveals dynamic immunodominance profiles of CD8⁺ T memory cells in convalescent COVID‐19 donors

Parallel detection of SARS‐CoV‐2 epitopes reveals dynamic immunodominance profiles of CD8⁺ T memory cells in convalescent COVID‐19 donors

Recombinant vaccines in 2022: a perspective from the cell factory

COVID-19 Vaccines: An Updated Overview of Different Platforms

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SARS-CoV-2–Specific Vaccine Candidates; the Contribution of Structural Vaccinology

Cited by 16 publications

References 94 publications

Parallel detection of SARS‐CoV‐2 epitopes reveals dynamic immunodominance profiles of CD8+ T memory cells in convalescent COVID‐19 donors

Parallel detection of SARS‐CoV‐2 epitopes reveals dynamic immunodominance profiles of CD8+ T memory cells in convalescent COVID‐19 donors

Recombinant vaccines in 2022: a perspective from the cell factory

COVID-19 Vaccines: An Updated Overview of Different Platforms

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Product

Resources

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Parallel detection of SARS‐CoV‐2 epitopes reveals dynamic immunodominance profiles of CD8⁺ T memory cells in convalescent COVID‐19 donors

Parallel detection of SARS‐CoV‐2 epitopes reveals dynamic immunodominance profiles of CD8⁺ T memory cells in convalescent COVID‐19 donors