Pre-pandemic SARS-CoV-2-specific IFN-γ and antibody responses were low in Ugandan samples and significantly reduced in HIV-positive specimens

Abstract

IntroductionWe investigated whether prior SARS-CoV-2-specific IFN-γ and antibody responses in Ugandan COVID-19 pre-pandemic specimens aligned to this population's low disease severity.MethodsWe used nucleoprotein (N), spike (S), NTD, RBD, envelope, membrane, SD1/2-directed IFN-γ ELISpots, and an S- and N-IgG antibody ELISA to screen for SARS-CoV-2-specific cross-reactivity.ResultsHCoV-OC43-, HCoV-229E-, and SARS-CoV-2-specific IFN-γ occurred in 23, 15, and 17 of 104 specimens, respectively. Cross-reactive IgG was more common against the nucleoprotein (7/110, 15.5%; p = 0.0016, Fishers' Exact) than the spike (3/110, 2.72%). Specimens lacking anti-HuCoV antibodies had higher rates of pre-epidemic SARS-CoV-2-specific IFN-γ cross-reactivity (p-value = 0.00001, Fishers’ exact test), suggesting that exposure to additional factors not examined here might play a role. SARS-CoV-2-specific cross-reactive antibodies were significantly less common in HIV-positive specimens (p=0.017; Fishers' Exact test). Correlations between SARS-CoV-2- and HuCoV-specific IFN-γ responses were consistently weak in both HIV negative and positive specimens.DiscussionThese findings support the existence of pre-epidemic SARS-CoV-2-specific cellular and humoral cross-reactivity in this population. The data do not establish that these virus-specific IFN-γ and antibody responses are entirely specific to SARS-CoV-2. Inability of the antibodies to neutralise SARS-CoV-2 implies that prior exposure did not result in immunity. Correlations between SARS-CoV-2 and HuCoV-specific responses were consistently weak, suggesting that additional variables likely contributed to the pre-epidemic cross-reactivity patterns. The data suggests that surveillance efforts based on the nucleoprotein might overestimate the exposure to SARS-CoV-2 compared to inclusion of additional targets, like the spike protein. This study, while limited in scope, suggests that HIV-positive people are less likely than HIV-negative people to produce protective antibodies against SARS-CoV-2.

The subdued post-boost spike-directed secondary IgG antibody response in Ugandan recipients of the Pfizer-BioNTech BNT162b2 vaccine has implications for local vaccination policies

“…We navigated the pragmatic challenges of a national mass vaccination campaign during a lockdown, which prioritised broad coverage over the assessment of prior infections. Recognising established data indicating the more extended durability of spike-directed IgG antibodies compared to N-IgG antibodies in this population ( 20 ) and elsewhere ( 13 ), we used baseline levels of both as proxies for prior exposure, acknowledging earlier studies revealing low pre-epidemic cross-reactivity in this population ( 21 ). This enabled us to examine the enhancement of spike-directed antibody responses in the Ugandan population following vaccination, offering a realistic depiction of the vaccine’s performance in this demographic under real-life conditions.…”

Immunological insights into COVID-19 in Southern Nigeria

“…Interestingly, sera collected prior to the COVID-19 pandemic have binding antibody responses to both N and S-RBD antigens and none had neutralizing antibody response to any of SARS-CoV-2 Spike PVs, unlike sera from COVID-19 symptomatic and asymptomatic participants with both binding and neutralizing antibody responses to SARS-CoV-2 PVs. The presence of cross-reactive binding antibody responses but with no neutralizing function have been observed in pre-pandemic sera in other African countries such as SierraLeone and Uganda ( 16 , 22 ). Future efforts to explore the non-neutralizing function of the pre-pandemic sera such as antibody dependent cytotoxicity (ADCC) and peptide arrays will help to determine the specificity and if pre-existing, cross-reactive bystander immunity may have played a role in reducing morbidity and mortality in Africans during the COVID-19 pandemic.…”

Persistent and robust antibody responses to ChAdOx1-S Oxford-AstraZeneca (ChAdOx1-S, Covishield) SARS-CoV-2 vaccine observed in Ugandans across varied baseline immune profiles

“…However, SSA studies on antibody responses to vaccination with ChAdOx1-S, Covishield are limited [ 4 , 5 ], yet important for understanding immune responses across diverse populations, to inform effective vaccination strategies. Available studies mostly focused on seroprevalence, concurrent cross-reactivity and prior exposure to other human coronaviruses [ 6 , 7 ], offering only a partial picture of vaccine-induced immunity. Inconsistencies have occurred across ChAdOx1-S, Covishield studies from UK and South Africa [ 8 ], possibly due to variable immune response to different SARS-CoV-2 variants [ 9 , 10 ].…”