Prevalence and functional profile of SARS-CoV-2 T cells in asymptomatic Kenyan adults
Taraz Samandari, Joshua B. Ongalo, Kimberly D. McCarthy, Richard K. Biegon, Philister A. Madiega, Anne Mithika, Joseph Orinda, Grace M. Mboya, Patrick Mwaura, Omu Anzala, Clayton Onyango, Fredrick O. Oluoch, Eric Osoro, Charles-Antoine Dutertre, Nicole Tan, Shou Kit Hang, Smrithi Hariharaputran, David C. Lye, Amy Herman-Roloff, Nina Le Bert, Antonio Bertoletti
Taraz Samandari, Joshua B. Ongalo, Kimberly D. McCarthy, Richard K. Biegon, Philister A. Madiega, Anne Mithika, Joseph Orinda, Grace M. Mboya, Patrick Mwaura, Omu Anzala, Clayton Onyango, Fredrick O. Oluoch, Eric Osoro, Charles-Antoine Dutertre, Nicole Tan, Shou Kit Hang, Smrithi Hariharaputran, David C. Lye, Amy Herman-Roloff, Nina Le Bert, Antonio Bertoletti
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Clinical Research and Public Health Infectious disease

Prevalence and functional profile of SARS-CoV-2 T cells in asymptomatic Kenyan adults

Abstract

Background SARS-CoV-2 infection in Africa has been characterized by a less severe disease profile than what has been observed elsewhere, but the profile of SARS-CoV-2–specific adaptive immunity in these mainly asymptomatic patients has not, to our knowledge, been analyzed.Methods We collected blood samples from residents of rural Kenya (n = 80), who had not experienced any respiratory symptoms or had contact with individuals with COVID-19 and had not received COVID-19 vaccines. We analyzed spike-specific antibodies and T cells specific for SARS-CoV-2 structural (membrane, nucleocapsid, and spike) and accessory (ORF3a, ORF7, ORF8) proteins. Pre-pandemic blood samples collected in Nairobi (n = 13) and blood samples from mild-to-moderately symptomatic COVID-19 convalescent patients (n = 36) living in the urban environment of Singapore were also studied.Results Among asymptomatic Africans, we detected anti-spike antibodies in 41.0% of the samples and T cell responses against 2 or more SARS-CoV-2 proteins in 82.5% of samples examined. Such a pattern was absent in the pre-pandemic samples. Furthermore, distinct from cellular immunity in European and Asian COVID-19 convalescents, we observed strong T cell immunogenicity against viral accessory proteins (ORF3a, ORF8) but not structural proteins, as well as a higher IL-10/IFN-γ cytokine ratio profile.Conclusions The high incidence of T cell responses against different SARS-CoV-2 proteins in seronegative participants suggests that serosurveys underestimate SARS-CoV-2 prevalence in settings where asymptomatic infections prevail. The functional and antigen-specific profile of SARS-CoV-2–specific T cells in African individuals suggests that environmental factors can play a role in the development of protective antiviral immunity.Funding US Centers for Disease Control and Prevention, Division of Global Health Protection; the Singapore Ministry of Health’s National Medical Research Council (COVID19RF3-0060, COVID19RF-001, COVID19RF-008, MOH-StaR17Nov-0001).

Authors

Taraz Samandari, Joshua B. Ongalo, Kimberly D. McCarthy, Richard K. Biegon, Philister A. Madiega, Anne Mithika, Joseph Orinda, Grace M. Mboya, Patrick Mwaura, Omu Anzala, Clayton Onyango, Fredrick O. Oluoch, Eric Osoro, Charles-Antoine Dutertre, Nicole Tan, Shou Kit Hang, Smrithi Hariharaputran, David C. Lye, Amy Herman-Roloff, Nina Le Bert, Antonio Bertoletti

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Figure 2

T cell response specific for different SARS-CoV-2 proteins in asymptomatic participants from Elgeyo Marakwet and Kisumu.

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T cell response specific for different SARS-CoV-2 proteins in asymptomat...
(A) Schematic representation of the 5 SARS-CoV-2–specific peptide pools containing 15 mer overlapping peptides spanning 30% of spike (S), entire membrane (M), and 50% NP, and complete accessory proteins ORF3a and ORF7/8 that were used in 18-hour whole-blood cultures. Levels of IFN-γ and IL-2 secreted in response to peptide stimulation were quantified in the plasma of the blood cultures. If peptide stimulation induced greater than 5 pg/mL cytokines (IFN-γ and/or IL-2) above the corresponding DMSO controls with 2 distinct peptide pools, the individual was considered positive for SARS-CoV-2–specific T cells. The percentages of individuals from (B) Elgeyo Marakwet and (C) Kisumu who were positive for SARS-CoV-2–specific T cells are shown in red. Heatmaps show the levels of cytokines (yellow to blue: IFN-γ; orange to blue: IL-2) released upon stimulation with the distinct peptide pools in each individual; HIV-positive individuals are indicated by a single asterisk (*); samples considered positive for T cells are indicated by a plus sign (+). Participants’ data are organized according to the level of neutralizing antibodies. (D) Percentage of individuals who tested positive or negative for SARS-CoV-2–specific T cells and neutralizing antibodies. Mem, membrane; ORF7+8, ORF7 and ORF8; pos, positive; neg, negative.