COVID-19 relapse associated with SARS-CoV-2 evasion from CD4+ T-cell recognition in an agammaglobulinemia patient

Morita, Ryo; Kubota‐Koketsu, Ritsuko; Lu, Xiuyuan; Sasaki, Tadahiro; Nakayama, Emi E.; Liu, Yuchen; Okuzaki, Daisuke; Motooka, Daisuke; Wing, James B.; Fujikawa, Y.; Ichida, Yuji; Amo, Kiyoko; Goto, Tetsushi; Hara, Junichi; Shirano, Michinori; Yamasaki, Satoshi; Shioda, Tatsuo

doi:10.1016/j.isci.2023.106685

Cited by 11 publications

(4 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Fifth, this report shows that the combined Spike, NSP-2, NSP-14 and Nucleoprotein-based mRNA/LNP vaccine elicited lungresident antigen-specific GzmB + CD4 + T CYT and GzmB + CD8 + T CYT , CD69 + IFN-γ + TNFα + CD4 + T EFF cells and CD69 + IFN-γ + TNFα + CD8 + T EFF cells that may have contributed to eliminating lungs-infected epithelial cells and interfered locally with virus replication in the lungs. This agrees with reports showing cross-reactive memory CD4 + and CD8 + T cells alone (without antibodies) may have protected SARS-CoV-2 infected patients with B-cell depletion from severe disease 77,78 and with non-human primates studied that showed that SARS-CoV-2-specific T cells reduced viral loads in macaques 79 . However, these might not be the only underlying immune mechanisms of the observed…”

Section: Discussionsupporting

confidence: 91%

A Broad-Spectrum Multi-Antigen mRNA/LNP-Based Pan-Coronavirus Vaccine Induced Potent Cross-Protective Immunity Against Infection and Disease Caused by Highly Pathogenic and Heavily Spike-Mutated SARS-CoV-2 Variants of Concern in the Syrian Hamster Model

Prakash,

Dhanushkodi,

Singer

et al. 2024

Preprint

View full text Add to dashboard Cite

The first-generation Spike-alone-based COVID-19 vaccines have successfully contributed to reducing the risk of hospitalization, serious illness, and death caused by SARS-CoV-2 infections. However, waning immunity induced by these vaccines failed to prevent immune escape by many variants of concern (VOCs) that emerged from 2020 to 2024, resulting in a prolonged COVID-19 pandemic. We hypothesize that a next-generation Coronavirus (CoV) vaccine incorporating highly conserved non-Spike SARS-CoV-2 antigens would confer stronger and broader cross-protective immunity against multiple VOCs. In the present study, we identified ten non-Spike antigens that are highly conserved in 8.7 million SARS-CoV-2 strains, twenty-one VOCs, SARS-CoV, MERS-CoV, Common Cold CoVs, and animal CoVs. Seven of the 10 antigens were preferentially recognized by CD8+ and CD4+ T-cells from unvaccinated asymptomatic COVID-19 patients, irrespective of VOC infection. Three out of the seven conserved non-Spike T cell antigens belong to the early expressed Replication and Transcription Complex (RTC) region, when administered to the golden Syrian hamsters, in combination with Spike, as nucleoside-modified mRNA encapsulated in lipid nanoparticles (LNP) (i.e., combined mRNA/LNP-based pan-CoV vaccine): (i) Induced high frequencies of lung-resident antigen-specific CXCR5+CD4+ T follicular helper (TFH) cells, GzmB+CD4+ and GzmB+CD8+ cytotoxic T cells (TCYT), and CD69+IFN-g+TNF-a+CD4+ and CD69+IFN-g+TNFa+CD8+ effector T cells (TEFF); and (ii) Reduced viral load and COVID-19-like symptoms caused by various VOCs, including the highly pathogenic B.1.617.2 Delta variant and the highly transmittable heavily Spike-mutated XBB1.5 Omicron sub-variant. The combined mRNA/LNP-based pan-CoV vaccine could be rapidly adapted for clinical use to confer broader cross-protective immunity against emerging highly mutated and pathogenic VOCs.

show abstract

Section: Discussionsupporting

confidence: 91%

A Broad-Spectrum Multi-Antigen mRNA/LNP-Based Pan-Coronavirus Vaccine Induced Potent Cross-Protective Immunity Against Infection and Disease Caused by Highly Pathogenic and Heavily Spike-Mutated SARS-CoV-2 Variants of Concern in the Syrian Hamster Model

Prakash,

Dhanushkodi,

Singer

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…★ , XBF, BA.2.86.1 and its descendent JN. ★ sublineages (convergent mutations: S: G446S/D) P126 BA.5.5 ORF1a:L3829F (nsp6) Morita et al 2023 [ 35 ] N/R Later Omicron BQ.1, XBB.2.3.8, and XBB.1.16 sublineages S: 138/145- (NTD, RDR2) Convergent deletion mutations by Hensley et al [ 36 ] and Sonnleitner et al 2022 [ 30 ] Y144- and similar deletions confer to resistance to NTD-directed mAbs [ 27 , 37 ] Alpha, Omicron BA.1, and later BQ.1, XBB (e.g., XBB.1. ★ , EG, FL, FU, GK, HK, HV), XBC.1.…”

Section: Resultsmentioning

confidence: 99%

Evidence of SARS-CoV-2 convergent evolution in immunosuppressed patients treated with antiviral therapies

Feng,

Reid,

Clark

et al. 2024

Virol J

View full text Add to dashboard Cite

Background The factors contributing to the accelerated convergent evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are not fully understood. Unraveling the contribution of viral replication in immunocompromised patients is important for the early detection of novel mutations and developing approaches to limit COVID-19. Methods We deep sequenced SARS-CoV-2 RNA from 192 patients (64% hospitalized, 39% immunosuppressed) and compared the viral genetic diversity within the patient groups of different immunity and hospitalization status. Serial sampling of 14 patients was evaluated for viral evolution in response to antiviral treatments. Results We identified hospitalized and immunosuppressed patients with significantly higher levels of viral genetic diversity and variability. Further evaluation of serial samples revealed accumulated mutations associated with escape from neutralizing antibodies in a subset of the immunosuppressed patients treated with antiviral therapies. Interestingly, the accumulated viral mutations that arose in this early Omicron wave, which were not common in the patient viral lineages, represent convergent mutations that are prevalent in the later Omicron sublineages, including the XBB, BA.2.86.1 and its descendent JN sublineages. Conclusions Our results illustrate the importance of identifying convergent mutations generated during antiviral therapy in immunosuppressed patients, as they may contribute to the future evolutionary landscape of SARS-CoV-2. Our study also provides evidence of a correlation between SARS-CoV-2 convergent mutations and specific antiviral treatments. Evaluating high-confidence genomes from distinct waves in the pandemic with detailed patient metadata allows for discerning of convergent mutations that contribute to the ongoing evolution of SARS-CoV-2.

show abstract

“…Despite regular IRT, patients with congenital agammaglobulinemia are more prone to viral respiratory infections which, in combination with chronic bacterial infection, predispose them to life-long pulmonary sequelae ( 20 – 22 ). COVID-19 exhibits prolonged and recurrent forms of disease in patients with inborn and acquired forms of hypogammaglobulinemia ( 23 – 26 ). Prolonged viral shedding of SARS-CoV2 after clinical resolution of infection in our patient could be due to impaired viral clearance and within-host genetics variations of the virus, as previously described in patients with antibody deficiency ( 24 , 27 , 28 ).…”

Section: Discussionmentioning

confidence: 99%

Case report: Rapidly progressive neurocognitive disorder with a fatal outcome in a patient with PU.1 mutated agammaglobulinemia

Miskovic,

Ljubicic,

Bonaci-Nikolic

et al. 2024

Front. Immunol.

View full text Add to dashboard Cite

IntroductionPU.1-mutated agammaglobulinemia (PU.MA) represents a recently described autosomal-dominant form of agammaglobulinemia caused by mutation of the SPI1 gene. This gene codes for PU.1 pioneer transcription factor important for the maturation of monocytes, B lymphocytes, and conventional dendritic cells. Only six cases with PU.MA, presenting with chronic sinopulmonary and systemic enteroviral infections, have been previously described. Accumulating literature evidence suggests a possible relationship between SPI1 mutation, microglial phagocytic dysfunction, and the development of Alzheimer’s disease (AD).Case descriptionWe present a Caucasian female patient born from a non-consanguineous marriage, who was diagnosed with agammaglobulinemia at the age of 15 years when the immunoglobulin replacement therapy was started. During the following seventeen years, she was treated for recurrent respiratory and intestinal infections. At the age of 33 years, the diagnosis of celiac-like disease was established. Five years later progressive cognitive deterioration, unstable gait, speech disturbances, and behavioral changes developed. Comprehensive microbiological investigations were negative, excluding possible infective etiology. Brain MRI, 18FDG-PET-CT, and neuropsychological testing were suggestive for a diagnosis of a frontal variant of AD. Clinical exome sequencing revealed the presence of a novel frameshift heterozygous variant c.441dup in exon 4 of the SPI1 gene. Despite intensive therapy, the patient passed away a few months after the onset of the first neurological symptoms.ConclusionWe describe the first case of PU.MA patient presenting with a rapidly progressive neurocognitive deterioration. The possible role of microglial dysfunction in patients with SPI1 mutation could explain their susceptibility to neurodegenerative diseases thus highlighting the importance of genetic testing in patients with inborn errors of immunity. Since PU.MA represents a newly described form of agammaglobulinemia, our case expands the spectrum of manifestations associated with SPI1 mutation.

show abstract

COVID-19 relapse associated with SARS-CoV-2 evasion from CD4+ T-cell recognition in an agammaglobulinemia patient

Cited by 11 publications

References 62 publications

A Broad-Spectrum Multi-Antigen mRNA/LNP-Based Pan-Coronavirus Vaccine Induced Potent Cross-Protective Immunity Against Infection and Disease Caused by Highly Pathogenic and Heavily Spike-Mutated SARS-CoV-2 Variants of Concern in the Syrian Hamster Model

A Broad-Spectrum Multi-Antigen mRNA/LNP-Based Pan-Coronavirus Vaccine Induced Potent Cross-Protective Immunity Against Infection and Disease Caused by Highly Pathogenic and Heavily Spike-Mutated SARS-CoV-2 Variants of Concern in the Syrian Hamster Model

Evidence of SARS-CoV-2 convergent evolution in immunosuppressed patients treated with antiviral therapies

Case report: Rapidly progressive neurocognitive disorder with a fatal outcome in a patient with PU.1 mutated agammaglobulinemia

Contact Info

Product

Resources

About