Vaccines and SARS-CoV-2 variants: the urgent need for a correlate of protection

Karim, Salim Safurdeen. Abdool

doi:10.1016/s0140-6736(21)00468-2

Cited by 54 publications

(53 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is evident that the fundamental components of the adaptive immune system (B cells, CD4 + T cells and CD8 + T cells) contribute to the control of SARS-CoV-2 infection (5)(6)(7)(8)(9)(10)(11). The exact correlates of protection remain to be elucidated (12,13), but circulating antibodies and memory immune cells are crucial in protection against COVID-19. Especially CORONAVIRUS SARS-CoV-2 variants of concern partially escape humoral but not T-cell responses in COVID-19 convalescent donors and vaccinees important are virus-specific neutralizing antibodies targeting the receptor binding domain (RBD) of the spike (S) protein, which correlate with presence of SARS-CoV-2 specific CD4 + circulating follicular helper T cells (cT FH ) (8,14) and can prevent the interaction between virus and the host cell (15).…”

Section: Introductionmentioning

confidence: 99%

SARS-CoV-2 variants of concern partially escape humoral but not T cell responses in COVID-19 convalescent donors and vaccine recipients

et al. 2021

View full text Add to dashboard Cite

The emergence of SARS-CoV-2 variants harboring mutations in the spike (S) protein has raised concern about potential immune escape. Here, we studied humoral and cellular immune responses to wild type SARS-CoV-2 and the B.1.1.7 and B.1.351 variants of concern in a cohort of 121 BNT162b2 mRNA-vaccinated health care workers (HCW). Twenty-three HCW recovered from mild COVID-19 disease and exhibited a recall response with high levels of SARS-CoV-2-specific functional antibodies and virus-specific T cells after a single vaccination. Specific immune responses were also detected in seronegative HCW after one vaccination, but a second dose was required to reach high levels of functional antibodies and cellular immune responses in all individuals. Vaccination-induced antibodies cross-neutralized the variants B.1.1.7 and B.1.351, but the neutralizing capacity and Fc-mediated functionality against B.1.351 was consistently 2- to 4-fold lower than to the homologous virus. In addition, peripheral blood mononuclear cells were stimulated with peptide pools spanning the mutated S regions of B.1.1.7 and B.1.351 to detect cross-reactivity of SARS-CoV-2-specific T cells with variants. Importantly, we observed no differences in CD4+ T-cell activation in response to variant antigens, indicating that the B.1.1.7 and B.1.351 S proteins do not escape T-cell-mediated immunity elicited by the wild type S protein. In conclusion, this study shows that some variants can partially escape humoral immunity induced by SARS-CoV-2 infection or BNT162b2 vaccination, but S-specific CD4+ T-cell activation is not affected by the mutations in the B.1.1.7 and B.1.351 variants.

show abstract

Section: Introductionmentioning

confidence: 99%

SARS-CoV-2 variants of concern partially escape humoral but not T cell responses in COVID-19 convalescent donors and vaccine recipients

et al. 2021

View full text Add to dashboard Cite

show abstract

“…SARS-CoV-2 strain analysis in participants in Phase 3 studies in South Africa has revealed that some vaccines show diminished protection against the B.1.351 variant strain, 17 including ChAdOx, 18 NVX-CoV2373, 19,20 and Ad26.COV2-S. 21 In addition, in vitro studies show that wild type S-specific antibodies elicited by mRNA-1273 and BNT162b1 show reduced binding to the B.1.351 variant S protein. [22][23][24] Taken together, these findings raise the concern that monovalent vaccines targeting only the S protein may not be the most optimal strategy for conferring protection against continually emerging variants.…”

Section: Introductionmentioning

confidence: 99%

Prime hAd5 Spike + Nucleocapsid Vaccination Induces Ten-Fold Increases in Mean T-Cell Responses in Phase 1 Subjects that are Sustained Against Spike Variants

Sieling

King

Wong

et al. 2021

Preprint

View full text Add to dashboard Cite

In response to the need for a safe, efficacious vaccine that provides broad immune protection against SARS-CoV-2 infection, we have developed a dual-antigen COVID-19 vaccine. The vaccine delivers both the viral spike (S) protein modified to increase cell-surface expression (S-Fusion) and the viral nucleocapsid (N) protein with an Enhanced T-cell Stimulation Domain (N-ETSD) to enhance MHC class I and II presentation and T-cell responses. The vaccine antigens are delivered using a human adenovirus serotype 5 (hAd5) platform with E1, E2b, and E3 regions deleted that has been shown in previous cancer vaccine studies to be effective in the presence of pre-existing hAd5 immunity. Here, we demonstrate the hAd5 S-Fusion + N-ETSD (hAd5 S + N) vaccine antigens when expressed by dendritic cells (DCs) of previously SARS-CoV-2-infected patients elicit Th1 dominant activation of autologous patient T cells, indicating the vaccine antigens have the potential for generating immune responses in patients previously infected or vaccinated. We further demonstrate that participants in our open-label Phase 1b study of the dual-antigen hAd5 S + N vaccine generate Th1 dominant S- and N-specific T cells after a single prime subcutaneous injection and that the magnitude of these responses were comparable to those seen for T cells from previously infected patients. We further present our in silico prediction of T-cell epitope HLA binding for both the first-wave SARS-CoV-2 ‘A’ strain and the K417N, E484K, and N501Y S as well as the T201I N variants that suggests T-cell responses to the hAd5 S + N vaccine will retain efficacy against these variants. These findings that the dual-antigen hAd5 S + N vaccine elicits SARS-CoV-2-relevant T-cell responses and that such cell-mediated protection is likely to be sustained against emerging variants supports the testing of this vaccine as a universal booster that would enhance and broaden existing immune protection conferred by currently approved S-based vaccines.

show abstract

“…Two mRNA-based vaccines, BNT162b2 (Pfizer–BioNTech, New York, NY, USA and Mainz, Rhineland-Palatinate, Germany), mRNA-1273 (Moderna, Cambridge, MA, USA), showed up to 95% efficacy, the adenovirus vector-based Ad26.CoV2.S (Johnson & Johnson, New Brunswick, NJ, USA) presented 72% efficacy in the USA but 57% in South Africa, while the chimpanzee adenovirus vector-based ChAdOx (AZD1222) (AstraZeneca, Cambridge, UK) presented 70% efficacy. Similarly, heterologous recombinant adenovirus vector-base Gam-COVID-Vac (Sputnik V, Moscow, Russia) demonstrated 91% efficacy in the preliminary phase 3 trials, while the protein-based vaccine NVX-CoV237 (Novavax, Gaithersburg, MD, USA) was 89% efficient in the U.K. but 49% in South Africa [ 14 , 15 , 16 , 17 , 18 ]. Two inactivated virus vaccines, CoronoVac (Sinovac, Beijing, China) and BBIBP-CorV (Sinopharm, China National Pharmaceutical Group, Beijing, China), passed through phase 3 clinical trials and were reported to show from 50% to 91% efficacy.…”

Section: Introductionmentioning

confidence: 99%

Multi-Subunit SARS-CoV-2 Vaccine Design Using Evolutionarily Conserved T- and B- Cell Epitopes

et al. 2021

View full text Add to dashboard Cite

The SARS-CoV-2 pandemic has created a public health crisis worldwide. Although vaccines against the virus are efficiently being rolled out, they are proving to be ineffective against certain emerging SARS-CoV-2 variants. The high degree of sequence similarity between SARS-CoV-2 and other human coronaviruses (HCoV) presents the opportunity for designing vaccines that may offer protection against SARS-CoV-2 and its emerging variants, with cross-protection against other HCoVs. In this study, we performed bioinformatics analyses to identify T and B cell epitopes originating from spike, membrane, nucleocapsid, and envelope protein sequences found to be evolutionarily conserved among seven major HCoVs. Evolutionary conservation of these epitopes indicates that they may have critical roles in viral fitness and are, therefore, unlikely to mutate during viral replication thus making such epitopes attractive candidates for a vaccine. Our designed vaccine construct comprises of twelve T and six B cell epitopes that are conserved among HCoVs. The vaccine is predicted to be soluble in water, stable, have a relatively long half-life, and exhibit low allergenicity and toxicity. Our docking results showed that the vaccine forms stable complex with toll-like receptor 4, while the immune simulations predicted that the vaccine may elicit strong IgG, IgM, and cytotoxic T cell responses. Therefore, from multiple perspectives, our multi-subunit vaccine design shows the potential to elicit a strong immune-protective response against SARS-CoV-2 and its emerging variants while carrying minimal risk for causing adverse effects.

show abstract

Vaccines and SARS-CoV-2 variants: the urgent need for a correlate of protection

Cited by 54 publications

References 10 publications

SARS-CoV-2 variants of concern partially escape humoral but not T cell responses in COVID-19 convalescent donors and vaccine recipients

SARS-CoV-2 variants of concern partially escape humoral but not T cell responses in COVID-19 convalescent donors and vaccine recipients

Prime hAd5 Spike + Nucleocapsid Vaccination Induces Ten-Fold Increases in Mean T-Cell Responses in Phase 1 Subjects that are Sustained Against Spike Variants

Multi-Subunit SARS-CoV-2 Vaccine Design Using Evolutionarily Conserved T- and B- Cell Epitopes

Contact Info

Product

Resources

About