SARS-COV-2 antibody responses to AZD1222 vaccination in West Africa

Abdullahi, Adam; Oladele, David; Owusu, Michael; Kemp, Steven A; Ayorinde, James; Salako, Abideen; Fink, Douglas; Ige, Fehintola; Ferreira, Isabella; Meng, Bo; Sylverken, Augustina Angelina; Onwuamah, Chika Kingsley; Boadu, Kwame Ofori; Osuolale, Kazeem Adewale; Frimpong, James Opoku; Abubakar, Rufai; Okuruawe, Azuka; Abdullahi, Haruna Wisso; Liboro, Gideon; Agyemang, Lawrence Duah; Ayisi-Boateng, Nana Kwame; Odubela, Oluwatosin; Ohihoin, Gregory; Ezechi, Oliver; Kamasah, Japhet Senyo; Ameyaw, Emmanuel; Arthur, Joshua; Boakye, Derrick K.; Owusu, Dorcas; Usman, Olagoke; Mogaji, Sunday; Dada, Adedamola; Agyei, George; Ebrahimi, Soraya; Gutierrez, Lourdes Ceron; Aliyu, Sani H; Döffinger, Rainer; Audu, Rosemary; Adegbola, Richard; Mlčochová, Petra; Phillips, Richard Odame; Solako, Babatunde Lawal; Rk, Gupta

doi:10.1038/s41467-022-33792-x

Cited by 20 publications

(33 citation statements)

References 45 publications

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“…26 Other studies in Africa also measured higher SARS-CoV-2 seroprevalence among vaccinated participants, higher neutralizing antibody titers among participants with infection and vaccination, and faster waning of antibodies post-vaccination among participants who had not been infected. 7,[27][28][29] These results support the recommendation for COVID-19 vaccination (including booster doses) regardless of past infection. COVID-19 vaccination campaigns were conducted throughout Zambia during the study period, but vaccine coverage among study participants was lower than the general population, possibly reflecting hesitancy toward vaccination during pregnancy, and only about 12% of the fully vaccinated population has received a booster dose.…”

Section: Discussionsupporting

confidence: 74%

“…Antenatal care (ANC) clinics have been utilized in several countries in Africa to monitor SARS-CoV-2 seroprevalence in a healthy population of women accessing healthcare services. [5][6][7][8][9] In Ethiopia, SARS-CoV-2 surveillance conducted in ANC clinics between April 2020 and March 2021 first detected SARS-CoV-2 antibodies in June 2020 and peaked at 11.8% in February 2021. 10 Repeated cross-sectional serosurveys in ANC clinics in Kenya found that most women were seropositive for SARS-CoV-2 antibodies by October 2021.…”

Section: Introductionmentioning

confidence: 99%

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Trends in SARS-CoV-2 seroprevalence among pregnant women attending first antenatal care visits in Zambia: a repeated cross-sectional survey, 2021-2022

Heilmann,

Tembo,

Fwoloshi

et al. 2024

Preprint

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BackgroundSARS-CoV-2 serosurveys help estimate the extent of transmission and guide allocation of COVID-19 vaccines. We measured SARS-CoV-2 seroprevalence among women attending ANC clinics to assess exposure trends over time in Zambia.MethodsWe conducted repeated cross-sectional surveys among pregnant women aged 15-49 years attending their first ANC visits in four districts of Zambia (two urban and two rural) during September 2021-September 2022. Serologic testing was done using a multiplex bead assay which detects IgG antibodies to the nucleocapsid protein and the spike protein receptor-binding domain (RBD). We calculated monthly SARS-CoV-2 seroprevalence by district. We also categorized seropositive results as infection alone, infection and vaccination, or vaccination alone based on COVID-19 vaccination status and anti-RBD and anti-nucleocapsid test results.FindingsAmong 8,304 participants, 5,296 (63.8%) were cumulatively seropositive for SARS-CoV-2 antibodies. SARS-CoV-2 seroprevalence primarily increased from September 2021 to September 2022 in three districts (Lusaka: 61.8-100.0%, Chongwe: 39.6-94.7%, Chipata: 56.5-95.0%), but in Chadiza, seroprevalence increased from 27.8% in September 2021 to 77.2% in April 2022 before gradually dropping to 56.6% in July 2022. Among 5,906 participants with a valid COVID-19 vaccination status, infection alone accounted for antibody responses in 77.7% (4,590) of participants.InterpretationMost women attending ANC had evidence of prior SARS-CoV-2 infection and most SARS-CoV-2 seropositivity was infection-induced. Capturing COVID-19 vaccination status and using a multiplex bead assay with anti-nucleocapsid and anti-RBD targets facilitated distinguishing infection-induced versus vaccine-induced antibody responses during a period of increasing COVID-19 vaccine coverage in Zambia. Declining seroprevalence in Chadiza may indicate waning antibodies and a need for booster vaccines. ANC clinics have a potential role in ongoing SARS-CoV-2 serosurveillance and can continue to provide insights into SARS-CoV-2 antibody dynamics to inform near real-time public health responses.

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Section: Discussionsupporting

confidence: 74%

Section: Introductionmentioning

confidence: 99%

Trends in SARS-CoV-2 seroprevalence among pregnant women attending first antenatal care visits in Zambia: a repeated cross-sectional survey, 2021-2022

Heilmann,

Tembo,

Fwoloshi

et al. 2024

Preprint

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“…Others have used varied methods to differentiate reinfection from initial infection ( 40 , 41 ). One macaque study showed a 7.6-fold rise in N-IgG antibody as indicative of reinfection ( 21 ), while a human West Africa study suggested a 7-fold rise ( 20 ); similar titre rises were also observed in studies from high-income settings ( 42 , 43 ). Our serological data from two SARS-CoV-2 reinfected patients with rt-PCR confirmation showed an 11-fold rise in N-IgG antibody concentration after reinfection.…”

Section: Methodsmentioning

confidence: 76%

“…Accordingly, antibodies directed against the S protein, particularly the RBD, are critical targets for developing vaccines and therapeutics (13)(14)(15) due to their positive associations with viral neutralisation titres (16)(17)(18)(19). On the other hand, the Nucleoprotein serves as the primary target in many serosurveillance test systems, and serological responses to N infer prior SARS-CoV-2 exposure (20)(21)(22).…”

Section: Introductionmentioning

confidence: 99%

Rapid, early, and potent Spike-directed IgG, IgM, and IgA distinguish asymptomatic from mildly symptomatic COVID-19 in Uganda, with IgG persisting for 28 months

Serwanga

Ankunda²,

Sembera³

et al. 2023

Front. Immunol.

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IntroductionUnderstanding how spike (S)-, nucleoprotein (N)-, and RBD-directed antibody responses evolved in mild and asymptomatic COVID-19 in Africa and their interactions with SARS-CoV-2 might inform development of targeted treatments and vaccines.MethodsHere, we used a validated indirect in-house ELISA to characterise development and persistence of S- and N-directed IgG, IgM, and IgA antibody responses for 2430 SARS-CoV-2 rt-PCR-diagnosed Ugandan specimens from 320 mild and asymptomatic COVID-19 cases, 50 uninfected contacts, and 54 uninfected non-contacts collected weekly for one month, then monthly for 28 months.ResultsDuring acute infection, asymptomatic patients mounted a faster and more robust spike-directed IgG, IgM, and IgA response than those with mild symptoms (Wilcoxon rank test, p-values 0.046, 0.053, and 0.057); this was more pronounced in males than females. Spike IgG antibodies peaked between 25 and 37 days (86.46; IQR 29.47-242.56 BAU/ml), were significantly higher and more durable than N- and RBD IgG antibodies and lasted for 28 months. Anti-spike seroconversion rates consistently exceeded RBD and nucleoprotein rates. Spike- and RBD-directed IgG antibodies were positively correlated until 14 months (Spearman’s rank correlation test, p-values 0.0001 to 0.05), although RBD diminished faster. Significant anti-spike immunity persisted without RBD. 64% and 59% of PCR-negative, non-infected non-contacts and suspects, exhibited baseline SARS-CoV-2 N-IgM serological cross-reactivity, suggesting undetected exposure or abortive infection. N-IgG levels waned after 787 days, while N-IgM levels remained undetectable throughout.DiscussionLower N-IgG seroconversion rates and the absence of N-IgM indicate that these markers substantially underestimate the prior exposure rates. Our findings provide insights into the development of S-directed antibody responses in mild and asymptomatic infections, with varying degrees of symptoms eliciting distinct immune responses, suggesting distinct pathogenic pathways. These longer-lasting data inform vaccine design, boosting strategies, and surveillance efforts in this and comparable settings.

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“…The antigenic shift represented by Omicron (B.1.1.529) resulted in a radically different virus characterized by multiple mutations in spike with extreme immune evasion of vaccines and increased transmissibility. [6][7][8][9][10][11][12][13] Immunological imprinting or original antigenic sin (OAS) 14 refers to a phenomenon where primary exposure to a pathogen shapes future immune responses to related strains [14][15][16] . As more antigenically distinct variants evolve, imprinting of the primary infection strain may limit the potency and breadth of humoral responses, instead favouring antibodies binding conserved epitopes.…”

Section: Introductionmentioning

confidence: 99%

Immune imprinting revealed by SARS-CoV-2 Omicron infection prior to vaccination

Gupta,

Abdullahi,

Onyemata

et al. 2024

Preprint

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Immune imprinting or original antigenic sin (OAS) originally referred to a phenomenon of suboptimal immune response to a repeat exposure to a virus that was antigenically distinct from the original virus infection. OAS has been implicated in higher mortality in young people during the 2009-10 H1N1 pandemic where the elderly (H1N1 exposure in childhood) appeared relatively well protected compared to younger individuals whose first influenza infection was not H1N1. Immune imprinting is part of a rapid recall system and is highly effective against a slowly evolving virus (drifting) but not antigenically shifting viruses such as influenza and SARS CoV-2. As predicted by OAS, suboptimal neutralization responses to the highly divergent SARS-COV-2 lineage Omicron have been observed in animal models and individuals previously vaccinated with primary course of ancestral (Wu-1) vaccine. Due to the rapid scale up of vaccine before emergence of the antigenically distinct Omicron variant, it is unknown whether immunological imprinting for occurs in the context of SARS-COV-2 infection itself. We longitudinally assessed humoral responses to primary two dose Ad26.COV2.S Wu-hu-1 based vaccination in a Nigerian population following the global emergence of Omicron. At study entry in Jan 2023, we found 93% and 58% of pre-vaccination participants previously exposed to ancestral Wu-1 and Omicron virus respectively by anti-N IgG and anti-receptor binding domain (RBD) IgG Wu-1 and Omicron -specific antibodies. In participants with no evidence of prior exposure to Omicron, neutralisation against Wu-1 was significantly higher than Omicron variants as expected. However, serum neutralisation titres in participants who were anti-RBD Omicron IgG positive were paradoxically 2-fold lower for Omicron BA.1 as compared to Wu-1. This is clear evidence for imprinted immunity from the ancestral pre-omicron lineage viruses, and remarkably these old responses to Wu-1 were able to dominate over more recent, likely multiple, Omicron lineage infections. Furthermore, in these participants with prior exposure to Omicron and evidence of imprinting, we observed that further Omicron infection and Wu-1 based vaccine was associated with boosting of responses across variants with equalisation of neutralisation titres for Wu-1 and Omicron variants. However, omicron responses did not surpass ancestral responses, suggesting persistence of imprinting and only partial mitigation. Although neutralization responses at high titres were observed post dose 1 vaccination against ancestral and Omicron variants BA.1, BA.2, BA.4 in nearly all participants, neutralisation against the highly immune evasive XBB recombinant variant remained substantially lower, with a second vaccine dose providing very modest boosting. These data highlight immune imprinting against SARS-CoV-2 prior to vaccination and its persistence thereafter. In present day unvaccinated populations where serum neutralisation responses to pre-Omicron variants dominate, use of an omicron variant based vaccine should be used in preference to Wu-1 based vaccine to override imprinting and provide broader protection for vulnerable populations such as the elderly or those with compromised immunity.

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SARS-COV-2 antibody responses to AZD1222 vaccination in West Africa

Cited by 20 publications

References 45 publications

Trends in SARS-CoV-2 seroprevalence among pregnant women attending first antenatal care visits in Zambia: a repeated cross-sectional survey, 2021-2022

Trends in SARS-CoV-2 seroprevalence among pregnant women attending first antenatal care visits in Zambia: a repeated cross-sectional survey, 2021-2022

Rapid, early, and potent Spike-directed IgG, IgM, and IgA distinguish asymptomatic from mildly symptomatic COVID-19 in Uganda, with IgG persisting for 28 months

Immune imprinting revealed by SARS-CoV-2 Omicron infection prior to vaccination

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