Proteomic Analysis of Mucosal and Systemic Responses to SARS-CoV-2 Antigen

Martinson, Neil; Gordhan, Bhavna G.; Petkov, Stefan; Pillay, Azure-Dee; Seiphetlo, Thabiso B.; Singh, Natasha; Otwombe, Kennedy; Lebina, Limakatso; Fredolini, Claudia; Chiodi, Francesca; Fox, Julie; Kana, Bavesh D; Herrera, Carolina

doi:10.3390/vaccines11020334

Cited by 4 publications

(3 citation statements)

References 32 publications

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“…A total of 18 adult participants aged between 18 and 70 years with a negative SARS-CoV-2 test prior to surgery were recruited to provide residual nasal or oral tissue. The baseline characteristics for the participants are described in Table 1 and in our recent study [ 17 ]. Briefly, the cohort was 61% male and 39% female with a median age of 40.2 years and an average BMI of 27.3.…”

Section: Resultsmentioning

confidence: 99%

“…These discordant observations confirm the value of ex vivo human tissue explant models in providing important biological correlates of viral pathogenesis. In the present study, we assessed whether SARS-CoV-2 strains were capable of infecting and replicating in nasal or oral tissue obtained from vaccinated and non-vaccinated individuals recruited in Johannesburg, South Africa [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of a human mucosal tissue explant model for SARS-CoV-2 replication

Gordhan,

Herrera,

Pillay

et al. 2023

PLoS ONE

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With the onset of COVID-19, the development of ex vivo laboratory models became an urgent priority to study host-pathogen interactions in response to the pandemic. In this study, we aimed to establish an ex vivo mucosal tissue explant challenge model for studying SARS-CoV-2 infection and replication. Nasal or oral tissue samples were collected from eligible participants and explants generated from the tissue were infected with various SARS-CoV-2 strains, including IC19 (lineage B.1.13), Beta (lineage B.1.351) and Delta (lineage B.1.617.2). A qRT-PCR assay used to measure viral replication in the tissue explants over a 15-day period, demonstrated no replication for any viral strains tested. Based on this, the ex vivo challenge protocol was modified by reducing the viral infection time and duration of sampling. Despite these changes, viral infectivity of the nasal and oral mucosa was not improved. Since 67% of the enrolled participants were already vaccinated against SARS-CoV-2, it is possible that neutralizing antibodies in explant tissue may have prevented the establishment of infection. However, we were unable to optimize plaque assays aimed at titrating the virus in supernatants from both infected and uninfected tissue, due to limited volume of culture supernatant available at the various collection time points. Currently, the reasons for the inability of these mucosal tissue samples to support replication of SARS-CoV-2 ex vivo remains unclear and requires further investigation.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Evaluation of a human mucosal tissue explant model for SARS-CoV-2 replication

Gordhan,

Herrera,

Pillay

et al. 2023

PLoS ONE

Self Cite

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“…In addition, attempts have been made to identify biomarkers related to efficient vaccine responses, and several associations between cytokine levels and SARS-CoV-2-specific humoral immune responses have been observed. Several studies with immunocompetent individuals have examined the correlates of SARS-CoV-2-specific humoral response and found changes in levels of M-CSF, IL-1α, IFN-γ, IL-1β, IL-10, IL-12p70, IL-6, IL-17A, IL-15, and IFN signaling-related cytokines (CXCL10, MCP-1, MCP-2, and MCP-3) to be correlated with SARS-CoV-2-specific antibody response in healthy volunteers [ 45 , 62 , 63 , 64 , 65 ]. Regarding PAD patients, several studies have examined the T cell response role in protection against SARS-CoV-2, showing IL-2 and/or IFN-γ secretion in response to pooled SARS-CoV-2 antigens [ 18 , 24 , 25 , 26 , 27 , 28 ].…”

Section: Introductionmentioning

confidence: 99%

Cytokine Response Following SARS-CoV-2 Antigen Stimulation in Patients with Predominantly Antibody Deficiencies

Lucane

Šlisere

Gersone

et al. 2023

Viruses

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Predominantly antibody deficiencies (PADs) are inborn disorders characterized by immune dysregulation and increased susceptibility to infections. Response to vaccination, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), may be impaired in these patients, and studies on responsiveness correlates, including cytokine signatures to antigen stimulation, are sparse. In this study, we aimed to describe the spike-specific cytokine response following whole-blood stimulation with SARS-CoV-2 spike peptides in patients with PAD (n = 16 with common variable immunodeficiency and n = 15 with selective IgA deficiency) and its relationship with the occurrence of coronavirus disease 2019 (COVID-19) during up to 10-month follow-up period. Spike-induced antibody and cytokine production was measured using ELISA (anti-spike IgG, IFN-γ) and xMAP technology (interleukin-1β (IL-1β), IL-4, IL-6, IL-10, IL-15, IL-17A, IL-21, TNF-α, TGF-β1). No difference was found in the production of cytokines between patients with PAD and controls. Anti-spike IgG and cytokine levels did not predict contraction of COVID-19. The only cytokine that distinguished between vaccinated and naturally infected unvaccinated PAD patients was IFN-γ (median 0.64 (IQR = 1.08) in vaccinated vs. 0.10 (IQR = 0.28) in unvaccinated). This study describes the spike-specific cytokine response to SARS-CoV-2 antigens, which is not predictive of contracting COVID-19 during the follow-up.

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