Natural killer cell responses during SARS-CoV-2 infection and vaccination in people living with HIV-1

Alrubayyi, Aljawharah; Touizer, Emma; Hameiri-Bowen, Dan; Charlton, Bethany; Gea-Mallorquí, Ester; Hussain, Noshin; da Costa, Kelly A. S.; Ford, Rosemarie; Rees-Spear, Chloe; Fox, Thomas A.; Williams, Ian; Waters, Laura; Barber, Tristan J.; Burns, Fiona; Kinloch, Sabine; Morris, Emma; Rowland-Jones, Sarah; McCoy, Laura E.; Peppa, Dimitra

doi:10.1038/s41598-023-45412-9

Cited by 5 publications

(1 citation statement)

References 96 publications

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“…It has been suggested that CD4/CD8 ratio may be useful to monitor HIV-1 infection and to improve clinical decision making. Although there is not clear increase in the rate of COVID-19 among PWH in comparison with the general population, low levels of CD4+ T cells have been related to severe forms of the disease ( 44 ), and low or inverted CD4/CD8 ratio reflects a decreased capacity to respond to SARS-CoV-2 ( 45 ). Accordingly, PWH with normal CD4/CD8 ratio should be able to respond efficiently to vaccination against COVID-19.…”

Section: Discussionmentioning

confidence: 99%

Pre-existing cell populations with cytotoxic activity against SARS-CoV-2 in people with HIV and normal CD4/CD8 ratio previously unexposed to the virus

Casado-Fernández,

Cantón,

Nasarre

et al. 2024

Front. Immunol.

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IntroductionHIV-1 infection may produce a detrimental effect on the immune response. Early start of antiretroviral therapy (ART) is recommended to preserve the integrity of the immune system. In fact, people with HIV (PWH) and normal CD4/CD8 ratio appear not to be more susceptible to severe forms of COVID-19 than the general population and they usually present a good seroconversion rate in response to vaccination against SARS-CoV-2. However, few studies have fully characterized the development of cytotoxic immune populations in response to COVID-19 vaccination in these individuals.MethodsIn this study, we recruited PWH with median time of HIV-1 infection of 6 years, median CD4/CD8 ratio of 1.0, good adherence to ART, persistently undetectable viral load, and negative serology against SARS-CoV-2, who then received the complete vaccination schedule against COVID-19. Blood samples were taken before vaccination against COVID-19 and one month after receiving the complete vaccination schedule. ResultsPWH produced high levels of IgG against SARS-CoV-2 in response to vaccination that were comparable to healthy donors, with a significantly higher neutralization capacity. Interestingly, the cytotoxic activity of PBMCs from PWH against SARS-CoV-2-infected cells was higher than healthy donors before receiving the vaccination schedule, pointing out the pre-existence of activated cell populations with likely unspecific antiviral activity. The characterization of these cytotoxic cell populations revealed high levels of Tgd cells with degranulation capacity against SARS-CoV-2-infected cells. In response to vaccination, the degranulation capacity of CD8+ T cells also increased in PWH but not in healthy donors.DiscussionThe full vaccination schedule against COVID-19 did not modify the ability to respond against HIV-1-infected cells in PWH and these individuals did not show more susceptibility to breakthrough infection with SARS-CoV-2 than healthy donors after 12 months of follow-up. These results revealed the development of protective cell populations with broad-spectrum antiviral activity in PWH with normal CD4/CD8 ratio and confirmed the importance of early ART and treatment adherence to avoid immune dysfunctions.

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Section: Discussionmentioning

confidence: 99%

Pre-existing cell populations with cytotoxic activity against SARS-CoV-2 in people with HIV and normal CD4/CD8 ratio previously unexposed to the virus

Casado-Fernández,

Cantón,

Nasarre

et al. 2024

Front. Immunol.

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A novel immunomodulating peptide with potential to complement oligodeoxynucleotide-mediated adjuvanticity in vaccination strategies

Agrez,

Chandler,

Thurecht

et al. 2024

Sci Rep

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The identification of adjuvants to improve vaccination efficacy is a major unmet need. One approach is to augment the functionality of dendritic cells (DCs) by using Toll-like receptor-9 (TLR9) agonists such as cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODNs) as adjuvants. Another approach is adjuvant selection based on production of bioactive interleukin-12 (IL-12). We report a D-peptide isomer, designated D-15800, that induces monocyte differentiation to the DC phenotype in vitro and more effectively stimulates IL-12p70 production upon T cell receptor (TCR) activation than the L-isomer. In the absence of TCR activation and either IL-12p70 or interleukin-2 production, only D-15800 activates CD4 + T and natural killer cells. In the presence of CpG ODN, D-15800 synergistically enhances production of interferon-alpha (IFN-α). Taken together with its biostability in human serum and depot retention upon injection, co-delivery of D-15800 with TLR9 agonists could serve to improve vaccine efficacy. Supplementary Information The online version contains supplementary material available at 10.1038/s41598-024-78150-7.

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The S2 subunit of spike encodes diverse targets for functional antibody responses to SARS-CoV-2

Guenthoer,

Garrett,

Lilly

et al. 2024

PLoS Pathog

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The SARS-CoV-2 virus responsible for the COVID-19 global pandemic has exhibited a striking capacity for viral evolution that drives continued evasion from vaccine and infection-induced immune responses. Mutations in the receptor binding domain of the S1 subunit of the spike glycoprotein have led to considerable escape from antibody responses, reducing the efficacy of vaccines and monoclonal antibody (mAb) therapies. Therefore, there is a need to interrogate more constrained regions of spike, such as the S2 subdomain. Here, we present a collection of S2 mAbs from two SARS-CoV-2 convalescent individuals that target multiple regions in S2, including regions outside of those commonly reported. One of the S2 mAbs, C20.119, which bound to a highly conserved epitope in the fusion peptide, was able to broadly neutralize across SARS-CoV-2 variants, SARS-CoV-1, and closely related zoonotic sarbecoviruses. The majority of the mAbs were non-neutralizing; however, many of them could mediate antibody-dependent cellular cytotoxicity (ADCC) at levels similar to the S1-targeting mAb S309 that was previously authorized for treatment of SARS-CoV-2 infections. Several of the mAbs with ADCC function also bound to spike trimers from other human coronaviruses (HCoVs), such as MERS-CoV and HCoV-HKU1. Our findings suggest S2 mAbs can target diverse epitopes in S2, including functional mAbs with HCoV and sarbecovirus breadth that likely target functionally constrained regions of spike. These mAbs could be developed for potential future pandemics, while also providing insight into ideal epitopes for eliciting a broad HCoV response.

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Natural killer cell responses during SARS-CoV-2 infection and vaccination in people living with HIV-1

Cited by 5 publications

References 96 publications

Pre-existing cell populations with cytotoxic activity against SARS-CoV-2 in people with HIV and normal CD4/CD8 ratio previously unexposed to the virus

Pre-existing cell populations with cytotoxic activity against SARS-CoV-2 in people with HIV and normal CD4/CD8 ratio previously unexposed to the virus

A novel immunomodulating peptide with potential to complement oligodeoxynucleotide-mediated adjuvanticity in vaccination strategies

The S2 subunit of spike encodes diverse targets for functional antibody responses to SARS-CoV-2

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