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Article: 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.

bioRxiv : the preprint server for biology

2024

Abstract: 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 ... ...

Abstract	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
Language	English
Publishing date	2024-02-15
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.02.14.580225
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Article ; Online: High frequencies of alpha common cold coronavirus/SARS-CoV-2 cross-reactive functional CD4

Coulon, Pierre-Gregoire / Prakash, Swayam / Dhanushkodi, Nisha R / Srivastava, Ruchi / Zayou, Latifa / Tifrea, Delia F / Edwards, Robert A / Figueroa, Cesar J / Schubl, Sebastian D / Hsieh, Lanny / Nesburn, Anthony B / Kuppermann, Baruch D / Bahraoui, Elmostafa / Vahed, Hawa / Gil, Daniel / Jones, Trevor M / Ulmer, Jeffrey B / BenMohamed, Lbachir

Frontiers in immunology

2024 Volume 15, Page(s) 1343716

Abstract: Background: Cross-reactive SARS-CoV-2-specific memory CD4: Methods: This study compares the antigen specificity, frequency, phenotype, and function of cross-reactive memory CD4: Results: Compared to severely ill COVID-19 patients and patients with ...

Abstract	Background: Cross-reactive SARS-CoV-2-specific memory CD4 Methods: This study compares the antigen specificity, frequency, phenotype, and function of cross-reactive memory CD4 Results: Compared to severely ill COVID-19 patients and patients with fatal COVID-19 outcomes, the asymptomatic COVID-19 patients displayed significantly: (i) higher rates of co-infection with the 229E alpha species of CCCs (α-CCC-229E); (ii) higher frequencies of cross-reactive functional CD134 Conclusions: These findings (i) support a crucial role of functional, poly-antigenic α-CCCs/SARS-CoV-2 cross-reactive memory CD4
MeSH term(s)	Humans ; COVID-19 ; SARS-CoV-2 ; CTLA-4 Antigen ; CD8-Positive T-Lymphocytes ; Common Cold ; Memory T Cells ; Hepatitis A Virus Cellular Receptor 2 ; Programmed Cell Death 1 Receptor ; CD4-Positive T-Lymphocytes ; Epitopes
Chemical Substances	CTLA-4 Antigen ; Hepatitis A Virus Cellular Receptor 2 ; Programmed Cell Death 1 Receptor ; Epitopes
Language	English
Publishing date	2024-03-28
Publishing country	Switzerland
Document type	Journal Article ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2024.1343716
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Article ; Online: Clinical and radiographic differentiation of lung nodules caused by mycobacteria and lung cancer: a case-control study.

Figueroa, Cesar J / Riedel, Elyn / Glickman, Michael S

BMC infectious diseases

2015 Volume 15, Page(s) 482

Abstract: Background: Lung nodules caused by mycobacteria can resemble lung cancer on chest imaging. The advent of lung cancer screening with low-dose Computed Tomography is accompanied by high false-positive rates, making it necessary to establish criteria to ... ...

Abstract	Background: Lung nodules caused by mycobacteria can resemble lung cancer on chest imaging. The advent of lung cancer screening with low-dose Computed Tomography is accompanied by high false-positive rates, making it necessary to establish criteria to differentiate malignant from benign nodules. Methods: We conducted a retrospective case-control study of 52 patients with mycobacterial lung nodules and 139 patients with lung cancer, diagnosed between 2010 and 2012. We compared clinical and radiographic characteristics to identify predictors of disease by univariate and multivariate analysis. The discriminatory power of maximum Standardized Uptake Values from Positron-Emission-Tomography was also evaluated. Results: Several variables were correlated with a diagnosis of mycobacterial infection or lung cancer on univariate analysis. Such variable include smoking status and history, lesion size and imaging evidence of tree-in-bud opacities, lymphadenopathy or emphysema on computed tomography. Upon author consensus, the most clinically-relevant variables were selected to undergo multivariate analysis. A history of current or former smoking [OR 4.4 (95 % CI 1.2-15.6) and 2.7 (95 % CI 1.1-6.8), respectively P = 0.04] was correlated with diagnoses of lung cancer. Contrarily, the presence of tree-in-bud opacities was less likely to be correlated with a diagnosis of malignancy [OR 0.04 (95 % CI 0.0-1.0), P = 0.05]. Additionally, higher maximum standardized uptake values from positron emission tomography were associated with malignancy on multivariate analysis [OR 1.1 (95 % CI 1.0-1.2), P = 0.04]; but the accuracy of the values in differentiating between diseases was only 0.67 as measured by the area under the curve. Lesion size was not independently associated with diagnosis [OR 0.5 (95 % CI 0.2-1.2), (P = 0.12)]. Conclusions: Establishing the likelihood of malignancy for lung nodules based on isolated clinical or radiographic criteria is difficult. Using the variables found in this study may allow clinicians to stratify patients into groups of high and low risk for malignancy, and therefore establish efficient diagnostic strategies.
MeSH term(s)	Adolescent ; Adult ; Aged ; Aged, 80 and over ; Case-Control Studies ; Child ; Child, Preschool ; Early Detection of Cancer ; Female ; Humans ; Lung/diagnostic imaging ; Lung/pathology ; Lung Neoplasms/diagnostic imaging ; Lung Neoplasms/pathology ; Male ; Middle Aged ; Multivariate Analysis ; Mycobacterium/pathogenicity ; Mycobacterium Infections/diagnostic imaging ; Mycobacterium Infections/microbiology ; Mycobacterium Infections/pathology ; Odds Ratio ; Positron-Emission Tomography ; Retrospective Studies ; Tomography, X-Ray Computed ; Young Adult
Language	English
Publishing date	2015-10-28
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ISSN	1471-2334
ISSN (online)	1471-2334
DOI	10.1186/s12879-015-1185-4
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Article ; Online: 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

bioRxiv

Abstract	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.
Keywords	covid19
Language	English
Publishing date	2024-02-15
Publisher	Cold Spring Harbor Laboratory
Document type	Article ; Online
DOI	10.1101/2024.02.14.580225
Database	COVID19

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Article ; Online: Genome-Wide B Cell, CD4

Prakash, Swayam / Srivastava, Ruchi / Coulon, Pierre-Gregoire / Dhanushkodi, Nisha R / Chentoufi, Aziz A / Tifrea, Delia F / Edwards, Robert A / Figueroa, Cesar J / Schubl, Sebastian D / Hsieh, Lanny / Buchmeier, Michael J / Bouziane, Mohammed / Nesburn, Anthony B / Kuppermann, Baruch D / BenMohamed, Lbachir

Journal of immunology (Baltimore, Md. : 1950)

2021 Volume 206, Issue 11, Page(s) 2566–2582

Abstract: Over the last two decades, there have been three deadly human outbreaks of coronaviruses (CoVs) caused by SARS-CoV, MERS-CoV, and SARS-CoV-2, which has caused the current COVID-19 global pandemic. All three deadly CoVs originated from bats and ... ...

Abstract	Over the last two decades, there have been three deadly human outbreaks of coronaviruses (CoVs) caused by SARS-CoV, MERS-CoV, and SARS-CoV-2, which has caused the current COVID-19 global pandemic. All three deadly CoVs originated from bats and transmitted to humans via various intermediate animal reservoirs. It remains highly possible that other global COVID pandemics will emerge in the coming years caused by yet another spillover of a bat-derived SARS-like coronavirus (SL-CoV) into humans. Determining the Ag and the human B cells, CD4
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Animals ; CD4-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/immunology ; Epitopes, T-Lymphocyte/genetics ; Epitopes, T-Lymphocyte/immunology ; Female ; Genome, Viral/immunology ; Genome-Wide Association Study ; Humans ; Male ; Middle Aged ; Middle East Respiratory Syndrome Coronavirus/genetics ; Middle East Respiratory Syndrome Coronavirus/immunology ; SARS Virus/genetics ; SARS Virus/immunology ; SARS-CoV-2/genetics ; SARS-CoV-2/immunology ; Viral Vaccines/genetics ; Viral Vaccines/immunology
Chemical Substances	Epitopes, T-Lymphocyte ; Viral Vaccines
Language	English
Publishing date	2021-04-28
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.2001438
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Article: Genome-Wide Asymptomatic B-Cell, CD4

bioRxiv : the preprint server for biology

2020

Abstract: Over the last two decades, there have been three deadly human outbreaks of Coronaviruses (CoVs) caused by emerging zoonotic CoVs: SARS-CoV, MERS-CoV, and the latest highly transmissible and deadly SARS-CoV-2, which has caused the current COVID-19 global ... ...

Abstract	Over the last two decades, there have been three deadly human outbreaks of Coronaviruses (CoVs) caused by emerging zoonotic CoVs: SARS-CoV, MERS-CoV, and the latest highly transmissible and deadly SARS-CoV-2, which has caused the current COVID-19 global pandemic. All three deadly CoVs originated from bats, the natural hosts, and transmitted to humans
Keywords	covid19
Language	English
Publishing date	2020-09-28
Publishing country	United States
Document type	Preprint
DOI	10.1101/2020.09.27.316018
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Article ; Online: High Frequencies of PD-1+TIM3+TIGIT+CTLA4+ Functionally Exhausted SARS-CoV-2-Specific CD4+ and CD8+ T Cells Associated with Severe Disease in Critically ill COVID-19 Patients

Coulon, Pierre-Gregoire A / Prakash, Swayam / Dhanushkodi, Nisha R / Srivastava, Ruchi / Zayou, Latifa / Tifrea, Delia F / Edwards, Robert A / Figueroa, Cesar J / Schubl, Sebastian D / Hsieh, Lanny / Nesburn, Anthony B / Kuppermann, Baruch D / BAHRAOUI, Elmostafa / Vahed, Hawa / Gil, Daniel / Jones, Trevor M / Ulmer, Jeffrey B / BENMOHAMED, LBACHIR

bioRxiv

Abstract: SARS-CoV-2-specific memory T cells that cross-react with common cold coronaviruses (CCCs) are present in both healthy donors and COVID-19 patients. However, whether these cross-reactive T cells play a role in COVID-19 pathogenesis versus protection ... ...

Abstract	SARS-CoV-2-specific memory T cells that cross-react with common cold coronaviruses (CCCs) are present in both healthy donors and COVID-19 patients. However, whether these cross-reactive T cells play a role in COVID-19 pathogenesis versus protection remain to be fully elucidated. In this study, we characterized cross-reactive SARS-CoV-2-specific CD4+ and CD8+ T cells, targeting genome-wide conserved epitopes in a cohort of 147 non-vaccinated COVID-19 patients, divided into six groups based on the degrees of disease severity. We compared the frequency, phenotype, and function of these SARS-CoV-2-specific CD4+ and CD8+ T cells between severely ill and asymptomatic COVID-19 patients and correlated this with alpha-CCCs and beta-CCCs co-infection status. Compared with asymptomatic COVID-19 patients, the severely ill COVID-19 patients and patients with fatal outcomes: (i) Presented a broad leukocytosis and a broad CD4+ and CD8+ T cell lymphopenia; (ii) Developed low frequencies of functional IFN-gamma-producing CD134+CD138+CD4+ and CD134+CD138+CD8+ T cells directed toward conserved epitopes from structural, non-structural and regulatory SARS-CoV-2 proteins; (iii) Displayed high frequencies of SARS-CoV-2-specific functionally exhausted PD-1+TIM3+TIGIT+CTLA4+CD4+ and PD-1+TIM3+TIGIT+CTLA4+CD8+ T cells; and (iv) Displayed similar frequencies of co-infections with beta-CCCs strains but significantly fewer co-infections with alpha-CCCs strains. Interestingly, the cross-reactive SARS-CoV-2 epitopes that recalled the strongest CD4+ and CD8+ T cell responses in unexposed healthy donors (HD) were the most strongly associated with better disease outcome seen in asymptomatic COVID-19 patients. Our results demonstrate that, the critically ill COVID-19 patients displayed fewer co-infection with alpha-CCCs strain, presented broad T cell lymphopenia and higher frequencies of cross reactive exhausted SARS-CoV-2-specific CD4+ and CD8+ T cells. In contrast, the asymptomatic COVID-19 patients, appeared to present more co-infections with alpha-CCCs strains, associated with higher frequencies of functional cross-reactive SARS-CoV-2-specific CD4+ and CD8+ T cells. These findings support the development of broadly protective, T-cell-based, multi-antigen universal pan-Coronavirus vaccines.
Keywords	covid19
Language	English
Publishing date	2022-01-31
Publisher	Cold Spring Harbor Laboratory
Document type	Article ; Online
DOI	10.1101/2022.01.30.478343
Database	COVID19

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Article ; Online: Ribosomal RNA gene sequencing for early diagnosis of Blastomyces dermatitidis infection.

Morjaria, Sejal / Otto, Caitlin / Moreira, Andre / Chung, Romy / Hatzoglou, Vaios / Pillai, Manju / Banaei, Niaz / Tang, Yi-Wei / Figueroa, Cesar J

International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases

2015 Volume 37, Page(s) 122–124

Abstract: Prompt detection and identification of fungal pathogens at the genus and species level is critical in order to provide timely antifungal therapy. Here, we highlight the vital role of molecular diagnostics in achieving a fast and definitive diagnosis of ... ...

Abstract	Prompt detection and identification of fungal pathogens at the genus and species level is critical in order to provide timely antifungal therapy. Here, we highlight the vital role of molecular diagnostics in achieving a fast and definitive diagnosis of disseminated blastomycosis in a diabetic patient presenting as a brain mass initially thought to be tumoral in nature. A broad-range PCR amplification and sequencing of the fungal ribosomal RNA genes on brain biopsy tissue obtained during elective craniotomy revealed a final microbial identification of Ajellomyces dermatitidis (telemorph of Blastomyces dermatitidis).
MeSH term(s)	Aged ; Blastomyces/genetics ; Blastomyces/isolation & purification ; Blastomycosis/diagnosis ; Blastomycosis/pathology ; Early Diagnosis ; Genes, rRNA ; Humans ; Male ; Polymerase Chain Reaction ; Sequence Analysis, RNA
Language	English
Publishing date	2015-08
Publishing country	Canada
Document type	Case Reports ; Journal Article
ZDB-ID	1331197-9
ISSN	1878-3511 ; 1201-9712
ISSN (online)	1878-3511
ISSN	1201-9712
DOI	10.1016/j.ijid.2015.06.017
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Article: Nontuberculous Mycobacterial Infections After Silicone Breast Implant Reconstruction Emphasize a Diversity of Infecting Mycobacteria.

Romero, Fabian A / Powell, Eleanor A / Babady, N Esther / Kaltsas, Anna / Figueroa, Cesar J / Pulitzer, Melissa / Mehrara, Babak J / Glickman, Michael S / Morjaria, Sejal

Open forum infectious diseases

2017 Volume 4, Issue 4, Page(s) ofx189

Abstract: Postsurgical skin and soft tissue infections (SSTIs) caused by nontuberculous mycobacteria (NTM) are uncommon, indolent, difficult to treat, and often mimic pyogenic bacterial infections. Here we present 3 cases of NTM infections following placement of ... ...

Abstract	Postsurgical skin and soft tissue infections (SSTIs) caused by nontuberculous mycobacteria (NTM) are uncommon, indolent, difficult to treat, and often mimic pyogenic bacterial infections. Here we present 3 cases of NTM infections following placement of silicone implants for reconstructive breast surgery. These cases emphasize the importance of a high index of suspicion for NTM in patients with SSI after a prosthetic reconstruction refractory to conventional antibiotic therapy and the importance of early investigation with mycobacterial-specific diagnostics.
Language	English
Publishing date	2017-09-02
Publishing country	United States
Document type	Journal Article
ZDB-ID	2757767-3
ISSN	2328-8957
ISSN	2328-8957
DOI	10.1093/ofid/ofx189
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Article ; Online: A case of protothecosis in a patient with multiple myeloma.

Figueroa, Cesar J / Camp, Brendan J / Varghese, George I / Miranda, Edwin / Querfeld, Christiane / Hassoun, Hani / Kamboj, Mini / Pulitzer, Melissa P

Journal of cutaneous pathology

2014 Volume 41, Issue 5, Page(s) 409–413

MeSH term(s)	Aged ; Humans ; Immunocompromised Host ; Infection/complications ; Infection/immunology ; Multiple Myeloma/complications ; Multiple Myeloma/immunology ; Prototheca ; Skin Diseases/complications ; Skin Diseases/immunology
Language	English
Publishing date	2014-05
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	187078-6
ISSN	1600-0560 ; 0303-6987
ISSN (online)	1600-0560
ISSN	0303-6987
DOI	10.1111/cup.12338
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