Neutralizing antibody activity in convalescent sera from infection in humans with SARS-CoV-2 and variants of concern

Dupont, Liane; Snell, Luke B; Graham, Carl; Seow, Jeffrey; Merrick, Blair; Lechmere, Thomas; Maguire, Thomas J. A.; Hallett, Sadie R.; Pickering, Suzanne; Charalampous, Themoula; Alcolea-Medina, Adela; Huettner, Isabella; Jiménez-Guardeño, Jose M.; Acors, Sam; Almeida, Nathália Alves Araújo de; Cox, Daniel; Dickenson, Ruth E.; Galão, Rui Pedro; Kouphou, Neophytos; Lista, Marie Jose; Ortega-Prieto, Ana Maria; Wilson, Harry; Winstone, Helena; Fairhead, Cassandra; Su, Jia; Nebbia, Gaia; Batra, Rahul; Neil, Stuart; Shankar-Hari, Manu; Edgeworth, Jonathan D; Malim, Michael H.; Doores, Katie J.

doi:10.1038/s41564-021-00974-0

Cited by 101 publications

(104 citation statements)

References 77 publications

(51 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We examined the potential plasma neutralization against the initial Seattle WA1 strain (WT) and SARS-CoV-2 variants of concern (B.1.1.7, B.1.351, B.1.617.2), and observed potent neutralization activity against WT in each of the studied samples. In agreement with published reports (34,35), weaker neutralization activities were seen against B.1.351 (beta), while neutralization of B1.1.7 (alpha) and B.1.617.2 (delta) was comparable to that of WT (36)(37)(38)(39). No difference was seen in the IC 50 titers against each of these four viruses between vaccine and convalescent groups.…”

Section: Discussionsupporting

confidence: 91%

Detection of Antibody Responses Against SARS-CoV-2 in Plasma and Saliva From Vaccinated and Infected Individuals

et al. 2021

View full text Add to dashboard Cite

Antibodies (Abs) are essential for the host immune response against SARS-CoV-2, and all the vaccines developed so far have been designed to induce Abs targeting the SARS-CoV-2 spike. Many studies have examined Ab responses in the blood from vaccinated and infected individuals. However, since SARS-CoV-2 is a respiratory virus, it is also critical to understand the mucosal Ab responses at the sites of initial virus exposure. Here, we examined plasma versus saliva Ab responses in vaccinated and convalescent patients. Although saliva levels were significantly lower, a strong correlation was observed between plasma and saliva total Ig levels against all SARS-CoV-2 antigens tested. Virus-specific IgG1 responses predominated in both saliva and plasma, while a lower prevalence of IgM and IgA1 Abs was observed in saliva. Antiviral activities of plasma Abs were also studied. Neutralization titers against the initial WA1 (D614G), B.1.1.7 (alpha) and B.1.617.2 (delta) strains were similar but lower against the B.1.351 (beta) strain. Spike-specific antibody-dependent cellular phagocytosis (ADCP) activities were also detected and the levels correlated with spike-binding Ig titers. Interestingly, while neutralization and ADCP potencies of vaccinated and convalescent groups were comparable, enhanced complement deposition to spike-specific Abs was noted in vaccinated versus convalescent groups and corresponded with higher levels of IgG1 plus IgG3 among the vaccinated individuals. Altogether, this study demonstrates the detection of Ab responses after vaccination or infection in plasma and saliva that correlate significantly, although Ig isotypic differences were noted. The induced plasma Abs displayed Fab-mediated and Fc-dependent functions with comparable neutralization and ADCP potencies, but a greater capacity to activate complement was elicited upon vaccination.

show abstract

Section: Discussionsupporting

confidence: 91%

Detection of Antibody Responses Against SARS-CoV-2 in Plasma and Saliva From Vaccinated and Infected Individuals

et al. 2021

View full text Add to dashboard Cite

show abstract

“…4 Currently approved vaccines, such as viral vector or mRNA vaccines, successfully limited the pandemic’s impact on global health. 5, 6 Most COVID-19 vaccines function by stimulating an immune response against the SARS-CoV-2 spike protein (S) 7–9 but, as the spike gene has gathered pronounced genetic variability, 10, 11 it is a common concern that the effectiveness of existing vaccines may be affected by those variants of SARS-CoV-2. 5, 6, 10, 12 At the time of writing, the World Health Organization (WHO) lists four variants of concern (VOC; Alpha, Beta, Gamma, Delta) and two variants of interest (VOI; Lambda, Mu).…”

Section: Figurementioning

confidence: 99%

Main protease mutants of SARS-CoV-2 variants remain susceptible to nirmatrelvir (PF-07321332)

Ullrich

Ekanayake

Otting

et al. 2021

Preprint

View full text Add to dashboard Cite

The COVID-19 pandemic continues to be a public health threat. Multiple mutations in the spike protein of emerging variants of SARS-CoV-2 appear to impact on the effectiveness of available vaccines. Specific antiviral agents are keenly anticipated but their efficacy may also be compromised in emerging variants. One of the most attractive coronaviral drug targets is the main protease (Mpro). A promising Mpro inhibitor of clinical relevance is the peptidomimetic PF-07321332. We expressed Mpro of five SARS-CoV-2 lineages (C.37 Lambda, B.1.1.318, B.1.2, B.1.351 Beta, P.2 Zeta), each of which carries a strongly prevalent missense mutation (G15S, T21I, L89F, K90R, L205V). Enzyme kinetics showed that these Mpro variants are similarly catalytically competent as the wildtype. We show that PF-07321332 has similar potency against the variants as against the wildtype. Our in vitro data suggest that the efficacy of specific Mpro inhibitors such as PF-07321332 is not compromised in current COVID-19 variants.Graphical Abstract

show abstract

“…Furthermore, to inhibit SARS-CoV-2 more efficiently, CD4 + T cells and CD8 + T cells play important roles in combating SARS-CoV-2 4 . Recent studies on humoral immunity induced by the vaccines provide evidence regarding the duration of the neutralizing antibody response 5 . Moreover, it is known that CD4 + T cells and CD8 + T cells, in addition to neutralizing Abs, can play an important role in inhibiting SARS-CoV-2 4 .…”

Section: Introductionmentioning

confidence: 99%

Identification of TCR repertoires in functionally competent cytotoxic T cells cross-reactive to SARS-CoV-2

et al. 2021

View full text Add to dashboard Cite

SARS-CoV-2-specific CD8+ T cells are scarce but detectable in unexposed healthy donors (UHDs). It remains unclear whether pre-existing human coronavirus (HCoV)-specific CD8+ T cells are converted to functionally competent T cells cross-reactive to SARS-CoV-2. Here, we identified the HLA-A24-high binding, immunodominant epitopes in SARS-CoV-2 spike region that can be recognized by seasonal coronavirus-specific CD8+ T cells from HLA-A24+ UHDs. Cross-reactive CD8+ T cells were clearly reduced in patients with hematological malignancy, who are usually immunosuppressed, compared to those in UHDs. Furthermore, we showed that CD8+ T cells in response to a selected dominant epitope display multifunctionality and cross-functionality across HCoVs in HLA-A24+ donors. Cross-reactivity of T-cell receptors isolated from them exhibited selective diversity at the single-cell level. Taken together, when stimulated well by immunodominant epitopes, selective pre-existing CD8+ T cells with high functional avidity may be cross-reactive against SARS-CoV-2.

show abstract

Neutralizing antibody activity in convalescent sera from infection in humans with SARS-CoV-2 and variants of concern

Cited by 101 publications

References 77 publications

Detection of Antibody Responses Against SARS-CoV-2 in Plasma and Saliva From Vaccinated and Infected Individuals

Detection of Antibody Responses Against SARS-CoV-2 in Plasma and Saliva From Vaccinated and Infected Individuals

Main protease mutants of SARS-CoV-2 variants remain susceptible to nirmatrelvir (PF-07321332)

Identification of TCR repertoires in functionally competent cytotoxic T cells cross-reactive to SARS-CoV-2

Contact Info

Product

Resources

About