Your browser doesn't support javascript.
Montrer: 20 | 50 | 100
Résultats 1 - 11 de 11
Filtre
1.
medrxiv; 2023.
Preprint Dans Anglais | medRxiv | ID: ppzbmed-10.1101.2023.10.28.23297714

Résumé

The COVID-19 post-pandemic period is characterised by infection waves of uncertain size (due to low rates of SARS-CoV-2 testing and notification), as well as limited uptake or global access to updated variant vaccines. Ongoing SARS-CoV-2 evolution has given rise to recombinant Omicron lineages that dominate globally (XBB.1), as well as the emergence of hypermutated variants (BA.2.86). In this context, durable and cross-reactive T-cell immune memory is critical for continued protection against severe COVID-19. We examined T-cell responses to SARS-CoV-2 approximately 1.5 years since Omicron first emerged. We describe sustained CD4+ and CD8+ spike-specific T-cell memory responses in healthcare workers in South Africa (n=39), most of whom had received 2 doses of Ad26.CoV2.S (Johnson & Johnson/Janssen) vaccine and experienced at least one SARS-CoV-2 infection. Spike-specific T cells were highly cross-reactive with all Omicron variants tested, including BA.2.86. Abundant non-spike (nucleocapsid and membrane)-specific T cells were detectable in most participants, augmenting the total T-cell resources available for protection. The bulk of SARS-CoV-2-specific T-cell responses had an early-differentiated phenotype, explaining their persistent nature. Thus, hybrid immunity leads to the accumulation of spike and non-spike T cells evident 3.5 years after the start of the pandemic, with preserved recognition of highly mutated SARS-CoV-2 variants. Long-term T-cell immune memory is likely to provide continued protection against severe outcomes of COVID-19. In BriefNesamari et al. investigate T-cell responses in the context of hybrid immunity 3.5 years after the start of the COVID-19 pandemic. They show that T-cell memory is highly durable and cross-reactive with recombinant variants XBB.1 and hypermutated BA.2.86. Abundant non-spike responses augment the overall T-cell response.


Sujets)
COVID-19
3.
medrxiv; 2023.
Preprint Dans Anglais | medRxiv | ID: ppzbmed-10.1101.2023.05.16.23290059

Résumé

SUMMARY SARS-CoV-2 infection in children typically results in asymptomatic or mild disease. There is a paucity of studies on antiviral immunity in African children. We investigated SARS-CoV-2-specific T cell responses in 71 unvaccinated asymptomatic South African children who were seropositive or seronegative for SARS-CoV-2. SARS-CoV-2-specific CD4+ T cell responses were detectable in 83% of seropositive and 60% of seronegative children. Although the magnitude of the CD4+ T cell response did not differ significantly between the two groups, their functional profiles were distinct, with SARS-CoV-2 seropositive children exhibiting a higher proportion of polyfunctional T cells compared to their seronegative counterparts. The frequency of SARS-CoV-2-specific CD4+ T cells in seronegative children was associated with the endemic human coronavirus (HCoV) HKU1 IgG response. Overall, the presence of SARS-CoV-2-responding T cells in seronegative children may result from cross-reactivity to endemic coronaviruses and could contribute to the relative protection from disease observed in SARS-CoV-2-infected children. Key words: SARS-CoV-2, Children, IgG responses, T cell response, Polyfunctional profile, endemic HCoV


Sujets)
COVID-19 , Syndrome respiratoire aigu sévère
4.
medrxiv; 2023.
Preprint Dans Anglais | medRxiv | ID: ppzbmed-10.1101.2023.03.15.23287288

Résumé

The impact of previous SARS-CoV-2 infection on the durability of Ad26.COV2.S vaccine-elicited responses, and the effect of homologous boosting has not been well explored. We followed a cohort of healthcare workers for 6 months after receiving the Ad26.COV2.S vaccine and a further one month after they received an Ad26.COV2.S booster dose. We assessed longitudinal spike-specific antibody and T cell responses in individuals who had never had SARS-CoV-2 infection, compared to those who were infected with either the D614G or Beta variants prior to vaccination. Antibody and T cell responses elicited by the primary dose were durable against several variants of concern over the 6 month follow-up period, regardless of infection history. However, at 6 months after first vaccination, antibody binding, neutralization and ADCC were as much as 33-fold higher in individuals with hybrid immunity compared to those with no prior infection. Antibody cross-reactivity profiles of the previously infected groups were similar at 6 months, unlike at earlier time points suggesting that the effect of immune imprinting diminishes by 6 months. Importantly, an Ad26.COV2.S booster dose increased the magnitude of the antibody response in individuals with no prior infection to similar levels as those with previous infection. The magnitude of spike T cell responses and proportion of T cell responders remained stable after homologous boosting, concomitant with a significant increase in long-lived early differentiated CD4 memory T cells. Thus, these data highlight that multiple antigen exposures, whether through infection and vaccination or vaccination alone, result in similar boosts after Ad26.COV2.S vaccination.


Sujets)
Déficit en protéine S , Infections , COVID-19
5.
researchsquare; 2022.
Preprint Dans Anglais | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-1170883.v1

Résumé

Neutralizing antibodies strongly correlate with protection for COVID-19 vaccines, but the corresponding memory B cells that form to protect against future infection are relatively understudied. Here we examine the effect of prior SARS-CoV-2 infection on the magnitude and phenotype of the B cell response to single dose Johnson and Johnson (Ad26.COV2.S) vaccination in South African health care workers. SARS-CoV-2 specific memory responses expand in response to Ad26.COV2.S and are maintained for the study duration (84 days) in all individuals. However, prior infection is associated with a greater frequency of these cells, a more prominent germinal center (GC) response, and increased class switched memory (CSM). These B cell features correlated with both neutralization and antibody-dependent cytotoxicity (ADCC) activity, and with the frequency of SARS-CoV-2 specific circulating T follicular helper cells (cTfh). In addition, the SARS-CoV-2 specific CD8+ T cell response correlated with increased memory B cell lung-homing, which was sustained in the infected group. Finally, although vaccination achieved equivalent B cell activation regardless of infection history, it was negatively impacted by age. These data show that phenotyping the B cell response to vaccination can provide mechanistic insight into the impact of prior infection on GC homing, CSM, cTfh, and neutralization activity. These data can provide early signals and mechanistic understanding to inform studies of vaccine boosting, durability, and co-morbidities.


Sujets)
COVID-19
6.
medrxiv; 2021.
Preprint Dans Anglais | medRxiv | ID: ppzbmed-10.1101.2021.12.26.21268380

Résumé

The SARS-CoV-2 Omicron variant has multiple Spike (S) protein mutations that contribute to escape from the neutralizing antibody responses, and reducing vaccine protection from infection. The extent to which other components of the adaptive response such as T cells may still target Omicron and contribute to protection from severe outcomes is unknown. We assessed the ability of T cells to react with Omicron spike in participants who were vaccinated with Ad26.CoV2.S or BNT162b2, and in unvaccinated convalescent COVID-19 patients (n = 70). We found that 70-80% of the CD4 and CD8 T cell response to spike was maintained across study groups. Moreover, the magnitude of Omicron cross-reactive T cells was similar to that of the Beta and Delta variants, despite Omicron harbouring considerably more mutations. Additionally, in Omicron-infected hospitalized patients (n = 19), there were comparable T cell responses to ancestral spike, nucleocapsid and membrane proteins to those found in patients hospitalized in previous waves dominated by the ancestral, Beta or Delta variants (n = 49). These results demonstrate that despite Omicron's extensive mutations and reduced susceptibility to neutralizing antibodies, the majority of T cell response, induced by vaccination or natural infection, cross-recognises the variant. Well-preserved T cell immunity to Omicron is likely to contribute to protection from severe COVID-19, supporting early clinical observations from South Africa.


Sujets)
Syndrome respiratoire aigu sévère , COVID-19
7.
medrxiv; 2021.
Preprint Dans Anglais | medRxiv | ID: ppzbmed-10.1101.2021.11.08.21266049

Résumé

The Janssen (Johnson & Johnson) Ad26.COV2.S non-replicating viral vector vaccine, which requires only a single dose and conventional cold chain storage, is a valuable tool for COVID-19 vaccination programs in resource-limited settings. Here we show that neutralizing and binding responses to Ad26.COV2.S vaccination are stable for 6 months post-vaccination, with responses highest against the ancestral vaccine-similar D614G variant. Secondly, using longitudinal samples from individuals who experienced clinically mild breakthrough infections 3-4 months after vaccination, we show dramatically boosted binding antibodies, Fc effector function and neutralization. These responses, which are cross-reactive against diverse SARS-CoV-2 variants and SARS-CoV-1, are of similar magnitude to humoral immune responses measured in severely ill, hospitalized donors. These data highlight the significant priming capacity of Ad26.COV2.S, and have implications for population immunity in areas where the single dose Ad26.COV2.S vaccine has been deployed.


Sujets)
COVID-19 , Douleur paroxystique
8.
medrxiv; 2021.
Preprint Dans Anglais | medRxiv | ID: ppzbmed-10.1101.2021.11.05.21265853

Résumé

SARS-CoV-2 variants of concern (VOCs) exhibit escape from neutralizing antibodies, causing concern about vaccine effectiveness. However, while non-neutralizing cytotoxic functions of antibodies are associated with decreased disease severity and vaccine protection, Fc effector function escape from VOCs is poorly defined. Furthermore, whether VOCs trigger Fc functions with altered specificity, as has been reported for neutralization, is unknown. Here, we demonstrate that the Beta VOC partially evades Fc effector activity in individuals infected with the original (D614G) variant. However, not all functions are equivalently affected, suggesting differential targeting by antibodies mediating distinct Fc functions. Furthermore, Beta infection triggered responses with significantly improved Fc cross-reactivity against global VOCs compared to either D614G infected or Ad26.COV2.S vaccinated individuals. This suggests that, as for neutralization, the infecting spike sequence impacts Fc effector function. These data have important implications for vaccine strategies that incorporate VOCs, suggesting these may induce broader Fc effector responses.


Sujets)
Réflexes anormaux , Infections
9.
medrxiv; 2021.
Preprint Dans Anglais | medRxiv | ID: ppzbmed-10.1101.2021.07.24.21261037

Résumé

The Johnson and Johnson Ad26.COV2.S single dose vaccine, designed as an emergency response to the pandemic, represents an attractive option for the scale-up of COVID-19 vaccination in resource-limited countries. We examined the effect of prior infection with ancestral (D614G) or Beta variants on Ad26.COV2.S immunogenicity approximately 28 days post-vaccination. We compared healthcare workers who were SARS-CoV-2 naive (n=20), to those infected during the first wave prior to the emergence of Beta (n=20), and those infected in the second wave (n=20), when Beta was the dominant variant. We demonstrate that a priming exposure from infection significantly increased the magnitude of spike binding antibodies, neutralizing antibodies and antibody-dependent cellular cytotoxicity activity (ADCC) against D614G, Beta and Delta variants. The magnitude of antibody boosting was similar in both waves, despite the longer time interval between wave 1 infection and vaccination (7 months), compared to wave 2 (2 months). ADCC and binding cross-reactivity was similar in both waves. However, neutralization cross-reactivity varied by wave, showing that the antibody repertoire was shaped by the spike sequence of the infecting variant. Robust CD4 and CD8 T cell responses to spike of similar or higher magnitude as those elicited by infection were induced after vaccination. In contrast to antibody responses, prior infection was not required for the generation of high magnitude T cell responses, and T cell recognition of the Beta variant was fully preserved. Therefore, Ad26.COV2.S vaccination following prior infection, even >6 months previously, may result in substantially enhanced protection against COVID-19, of particular relevance in settings of high SARS-CoV-2 seroprevalence. Furthermore, the dominant impact of the infecting variant on neutralization breadth after vaccination has important implications for the design of second-generation vaccines based on variants of concern.


Sujets)
Déficit en protéine S , Encéphalomyélite aigüe disséminée , Effets secondaires indésirables des médicaments , COVID-19
10.
medrxiv; 2021.
Preprint Dans Anglais | medRxiv | ID: ppzbmed-10.1101.2021.06.03.21258307

Résumé

SARS-CoV-2 variants have emerged that escape neutralization and potentially impact vaccine efficacy. T cell responses play a role in protection from reinfection and severe disease, but the potential for spike mutations to affect T cell immunity is poorly studied. We assessed both neutralizing antibody and T cell responses in 44 South African COVID-19 patients infected either with B.1.351, now dominant in South Africa, or infected prior to its emergence (first wave), to provide an overall measure of immune evasion. We show for the first time that robust spike-specific CD4 and CD8 T cell responses were detectable in B.1.351-infected patients, similar to first wave patients. Using peptides spanning only the B.1.351 mutated regions, we identified CD4 T cell responses targeting the wild type peptides in 12/22 (54.5%) first wave patients, all of whom failed to recognize corresponding B.1.351-mutated peptides (p=0.0005). However, responses to the mutated regions formed only a small proportion (15.7%) of the overall CD4 response, and few patients (3/44) mounted CD8 responses that targeted the mutated regions. First wave patients showed a 12.7 fold reduction in plasma neutralization of B.1.351. This study shows that despite loss of recognition of immunodominant CD4 epitope(s), overall CD4 and CD8 T cell responses to B.1.351 are preserved. These observations may explain why, despite substantial loss of neutralizing antibody activity against B.1.351, several vaccines have retained the ability to protect against severe COVID-19 disease.


Sujets)
COVID-19
11.
biorxiv; 2021.
Preprint Dans Anglais | bioRxiv | ID: ppzbmed-10.1101.2021.03.06.434193

Résumé

Neutralization escape by SARS-CoV-2 variants, as has been observed in the 501Y.V2 (B.1.351) variant, has impacted the efficacy of first generation COVID-19 vaccines. Here, the antibody response to the 501Y.V2 variant was examined in a cohort of patients hospitalized with COVID-19 in early 2021 - when over 90% of infections in South Africa were attributed to 501Y.V2. Robust binding and neutralizing antibody titers to the 501Y.V2 variant were detected and these binding antibodies showed high levels of cross-reactivity for the original variant, from the first wave. In contrast to an earlier study where sera from individuals infected with the original variant showed dramatically reduced potency against 501Y.V2, sera from 501Y.V2-infected patients maintained good cross-reactivity against viruses from the first wave. Furthermore, sera from 501Y.V2-infected patients also neutralized the 501Y.V3 (P.1) variant first described in Brazil, and now circulating globally. Collectively these data suggest that the antibody response in patients infected with 501Y.V2 has a broad specificity and that vaccines designed with the 501Y.V2 sequence may elicit more cross-reactive responses.


Sujets)
COVID-19 , Syndrome des cassures de Nijmegen
SÉLECTION CITATIONS
Détails de la recherche