Conservation and Evolution of Antigenic Determinants of SARS-CoV-2: An Insight for Immune Escape and Vaccine Design

Jaiswal, Varun; Lee, Hae‐Jeung

doi:10.3389/fimmu.2022.832106

Cited by 8 publications

(7 citation statements)

References 37 publications

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“…Jaiswal et al mathematically (in-house developed PERL scripts) revealed sets of epitopes on the S1 subunit around 453 to 538 that interact with the ACE and are 99% conserved among the variants of SARS-CoV-2 [ 116 ]. Their study further identified conserved common neutralizing epitopes on the SARS-CoV-2, including YLTPGDSSSGWTAGAAAYYV (247–267 aa), TFKCYGVSPTKLNDL (376–390 aa) on S1 and LNEVAKNLNESLIDLQELGK (1186–1205 aa) on the S2 [ 116 ].…”

Section: Sars-cov-2 S Conserved Regions As a Potential Target For Vac...mentioning

confidence: 99%

Significance of Conserved Regions in Coronavirus Spike Protein for Developing a Novel Vaccine against SARS-CoV-2 Infection

Olukitibi

Warner

et al. 2023

Vaccines

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Over the years, several distinct pathogenic coronaviruses have emerged, including the pandemic SARS-CoV-2, which is difficult to curtail despite the availability of licensed vaccines. The difficulty in managing SARS-CoV-2 is linked to changes in the variants’ proteins, especially in the spike protein (SP) used for viral entry. These mutations, especially in the SP, enable the virus to evade immune responses induced by natural infection or vaccination. However, some parts of the SP in the S1 subunit and the S2 subunit are considered conserved among coronaviruses. In this review, we will discuss the epitopes in the SARS-CoV-2 S1 and S2 subunit proteins that have been demonstrated by various studies to be conserved among coronaviruses and may be immunogenic for the development of a vaccine. Considering the higher conservancy of the S2, we will further discuss the likely challenges that could limit the S2 subunit from inducing robust immune responses and the promising approaches to increase its immunogenicity.

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Section: Sars-cov-2 S Conserved Regions As a Potential Target For Vac...mentioning

confidence: 99%

Significance of Conserved Regions in Coronavirus Spike Protein for Developing a Novel Vaccine against SARS-CoV-2 Infection

Olukitibi

Warner

et al. 2023

Vaccines

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“…Considering the ineffectiveness of current SARS-CoV-2 antibody-based immunotherapy due to the development of novel mutations and the immune escape of the VOCs ( 52 ), other therapeutic options are warranted. Adoptive SARS-CoV-2 specific T cell therapy represents an attractive therapeutic option in which viral immune escape is likely to be avoided as the recognized T cell epitopes are well conserved among the emerging SARS-CoV-2 variants ( 25 ). Moreover, adoptive cellular therapy with ex-vivo expanded specific T cells against other viruses (CMV, EBV, Adv, HHV6, and BKV) has been demonstrated to have efficacy in combating severe viral diseases in patients with immunodeficiency ( 53 ).…”

Section: Discussionmentioning

confidence: 99%

“…demonstrated that T cell memory response in COVID-19 vaccinated, and convalescent individuals could be more persistent than antibody response leading to a more durable source of protection ( 23 , 24 ). Furthermore, recent studies indicated that T cell response and functionality against SARS-CoV-2 were not affected by the mutations or antigenic variation of the emerging variants of concern as the humoral response ( 25 – 27 ). These findings provide direct evidence that a lack or impairment of the T cell response could be associated with an elevated risk of SARS-CoV-2 infection and severe COVID-19 disease outcome.…”

Section: Introductionmentioning

confidence: 99%

Persistence of spike-specific immune responses in BNT162b2-vaccinated donors and generation of rapid ex-vivo T cells expansion protocol for adoptive immunotherapy: A pilot study

et al. 2023

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IntroductionThe BNT162b2 mRNA-based vaccine has shown high efficacy in preventing COVID-19 infection but there are limited data on the types and persistence of the humoral and T cell responses to such a vaccine.MethodsHere, we dissect the vaccine-induced humoral and cellular responses in a cohort of six healthy recipients of two doses of this vaccine.Results and discussionOverall, there was heterogeneity in the spike-specific humoral and cellular responses among vaccinated individuals. Interestingly, we demonstrated that anti-spike antibody levels detected by a novel simple automated assay (Jess) were strongly correlated (r=0.863, P<0.0001) with neutralizing activity; thus, providing a potential surrogate for neutralizing cell-based assays. The spike-specific T cell response was measured with a newly modified T-spot assay in which the high-homology peptide-sequences cross-reactive with other coronaviruses were removed. This response was induced in 4/6 participants after the first dose, and all six participants after the second dose, and remained detectable in 4/6 participants five months post-vaccination. We have also shown for the first time, that BNT162b2 vaccine enhanced T cell responses also against known human common viruses. In addition, we demonstrated the efficacy of a rapid ex-vivo T cell expansion protocol for spike-specific T cell expansion to be potentially used for adoptive-cell therapy in severe COVID-19, immunocompromised individuals, and other high-risk groups. There was a 9 to 13.7-fold increase in the number of expanded T cells with a significant increase of anti-spike specific response showing higher frequencies of both activation and cytotoxic markers. Interestingly, effector memory T cells were dominant in all four participants’ CD8+ expanded memory T cells; CD4+ T cells were dominated by effector memory in 2/4 participants and by central memory in the remaining two participants. Moreover, we found that high frequencies of CD4+ terminally differentiated memory T cells were associated with a greater reduction of spike-specific activated CD4+ T cells. Finally, we showed that participants who had a CD4+ central memory T cell dominance expressed a high CD69 activation marker in the CD4+ activated T cells.

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Section: Sars-cov-2 S Conserved Regions As a Potential Target For Vac...mentioning

confidence: 99%

“…Jaiswal et al mathematically (in-house developed PERL scripts) revealed sets of epitopes on the S1 subunit around 453 to 538 that interact with the ACE are 99% conserved among the variants of SARS-CoV-2 [106]. Their study further identified conserved common neutralizing epitopes on the SARS-CoV-2 including YLTPGDSSSGWTAGAAAYYV (247-267 aa), TFKCYGVSPTKLNDL (376-390 aa) on S1 and LNEVAKNLNESLID-LQELGK (1186-1205 aa) on the S2 [106]. A recent immunoinformatic study predicted conserved and highly immunogenic CTL-induced epitopes on S1 VRFPNITNL (327-335 aa), and PYRVVVLSF (507 -515 aa) (Table 1), while the CTL-induced epitopes on S2 were identified to be VVFLHVTYV (1060-1068 aa) and GVVFLHVTY (1059-1067 aa) (Table 2) [107].…”

Section: Sars-cov-2 S Conserved Regions As a Potential Target For Vac...mentioning

confidence: 99%

Significance of Conserved Regions in Coronavirus Spike Protein for Developing a Novel Vaccine against SARS-Cov-2 Infection

Olukitibi¹,

Ao²,

Warner³

et al. 2023

Preprint

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Over the years, several distinct pathogenic coronaviruses have emerged, including the pandemic SARS-CoV-2 which is difficult to curtail despite the availability of licensed vaccines. The difficulty in managing SARS-CoV-2 is linked to changes in the variants’ proteins, especially in the spike protein (S) used for viral entry. These mutations, especially in the S, enable the virus to evade the immune responses induced by natural infection or vaccination. However, some parts of the SP in the S1 subunit and the S2 subunit are considered conserved among coronaviruses. In this review, we will discuss the epitopes in the SARS-CoV-2 S1 and S2 subunit proteins that have been demonstrated by various studies to be conserved among coronaviruses and may be immunogenic for the development of vaccine. Considering the higher conservancy of the S2, we will further discuss the likely challenges that could limit the S2 subunit from inducing robust immune responses and the promising approaches to increase their immunogenicity.

show abstract

Conservation and Evolution of Antigenic Determinants of SARS-CoV-2: An Insight for Immune Escape and Vaccine Design

Cited by 8 publications

References 37 publications

Significance of Conserved Regions in Coronavirus Spike Protein for Developing a Novel Vaccine against SARS-CoV-2 Infection

Significance of Conserved Regions in Coronavirus Spike Protein for Developing a Novel Vaccine against SARS-CoV-2 Infection

Persistence of spike-specific immune responses in BNT162b2-vaccinated donors and generation of rapid ex-vivo T cells expansion protocol for adoptive immunotherapy: A pilot study

Significance of Conserved Regions in Coronavirus Spike Protein for Developing a Novel Vaccine against SARS-Cov-2 Infection

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