Immunoinformatics prediction of potential immunodominant epitopes from human coronaviruses and association with autoimmunity

Background: Streptococcus pneumoniae is a leading cause of pneumonia, mostly in children less than five years and elderly people. Although the pneumoniae polysaccharide vaccine (PPV) and pneumonia conjugate vaccines (PCV) are the efficient pneumococcal vaccine in adult and children groups, but the serotype replacement of S. pneumoniae strains causes the reduction in the efficacy of PPV and PCV vaccines. Epitope-based vaccines are a promising alternative to the present capsular antigen vaccines. Methods: In this study, we evaluated cellular and humoral immune responses induced by our novel designed multi-epitope vaccine in BALB/c mice. CD8+ cytolytic T lymphocytes (CTLs) epitopes were selected from PspA and CbpA antigens, and CD4+ helper T lymphocytes (HTLs) epitopes were chosen from PhtD and PiuA antigens. PorB, the TLR2 agonist, as an adjuvant, was employed to increase the immunogenicity of the vaccine. Results and conclusion: The high levels of specific anti-peptide vaccine IgG and an increase in the level of IgG2 in the vaccinated group demonstrated our vaccine could elicit a robust antibody production. The significant increase in IFN-γ, IL-2, TNF-α, IL-4, IL-6, and decrease in IL-10 showed that, the designed vaccine could be proposed as the efficient preventative pneumococcal vaccine in the mouse model.

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The Seasonal End of Human Coronavirus Hospital Admissions with Implications for SARS-CoV-2 (Preprint)

10.2196/preprints.21223 ◽

2020 ◽

Author(s):

Alan T Evangelista

Keyword(s):

Hospital Admissions ◽

Disease Incidence ◽

Influenza Viruses ◽

Seasonal Effects ◽

Human Coronavirus ◽

Enveloped Virus ◽

Multiplex Pcr Assay ◽

Contact Transmission ◽

Human Coronaviruses

UNSTRUCTURED The seasonality of influenza viruses and endemic human coronaviruses was tracked over an 8-year period to assess key epidemiologic reduction points in disease incidence for an urban area in the northeast United States. Patients admitted to a pediatric hospital with worsening respiratory symptoms were tested using a multiplex PCR assay from nasopharyngeal swabs. The additive seasonal effects of outdoor temperatures and indoor relative humidity (RH) were evaluated. The 8-year average peak activity of human coronaviruses occurred in the first week of January, when droplet and contact transmission was enabled by the low indoor RH of 20-30%. Previous studies have shown that an increase in RH to 50% has been associated with markedly reduced viability and transmission of influenza virus and animal coronaviruses. As disease incidence was reduced by 50% in early March, to 75% in early April, to greater than 99% at the end of April, a relationship was observed from colder temperatures in January with a low indoor RH to a gradual increase in outdoor temperatures in April with an indoor RH of 45-50%. As a lipid-bound, enveloped virus with similar size characteristics to endemic human coronaviruses, SARS-CoV-2 should be subject to the same dynamics of reduced viability and transmission with increased humidity. In addition to the major role of social distancing, the transition from lower to higher indoor RH with increasing outdoor temperatures could have an additive effect on the decrease in SARS-CoV-2 cases in May. Over the 8-year period of this study, human coronavirus activity was either zero or >99% reduction in the months of June through September, and the implication would be that SARS-Cov-2 may follow a similar pattern. INTERNATIONAL REGISTERED REPORT RR2-doi.org/10.1101/2020.05.15.20103416

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Human Coronaviruses: Counteracting the Damage by Storm

Viruses ◽

10.3390/v13081457 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1457

Author(s):

Dewald Schoeman ◽

Burtram C. Fielding

Keyword(s):

Immune Response ◽

Severe Disease ◽

Antiviral Agents ◽

The Elderly ◽

Highly Pathogenic ◽

Vaccine Responses ◽

Cell Mediated Immune Response ◽

Inhibition Antibody ◽

A Cell ◽

Human Coronaviruses

Over the past 18 years, three highly pathogenic human (h) coronaviruses (CoVs) have caused severe outbreaks, the most recent causative agent, SARS-CoV-2, being the first to cause a pandemic. Although much progress has been made since the COVID-19 pandemic started, much about SARS-CoV-2 and its disease, COVID-19, is still poorly understood. The highly pathogenic hCoVs differ in some respects, but also share some similarities in clinical presentation, the risk factors associated with severe disease, and the characteristic immunopathology associated with the progression to severe disease. This review aims to highlight these overlapping aspects of the highly pathogenic hCoVs—SARS-CoV, MERS-CoV, and SARS-CoV-2—briefly discussing the importance of an appropriately regulated immune response; how the immune response to these highly pathogenic hCoVs might be dysregulated through interferon (IFN) inhibition, antibody-dependent enhancement (ADE), and long non-coding RNA (lncRNA); and how these could link to the ensuing cytokine storm. The treatment approaches to highly pathogenic hCoV infections are discussed and it is suggested that a greater focus be placed on T-cell vaccines that elicit a cell-mediated immune response, using rapamycin as a potential agent to improve vaccine responses in the elderly and obese, and the potential of stapled peptides as antiviral agents.

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Drivers of Infectious Disease Seasonality: Potential Implications for COVID-19

Journal of Biological Rhythms ◽

10.1177/0748730420987322 ◽

2021 ◽

pp. 074873042098732

Author(s):

N. Kronfeld-Schor ◽

T. J. Stevenson ◽

S. Nickbakhsh ◽

E. S. Schernhammer ◽

X. C. Dopico ◽

...

Keyword(s):

Infectious Disease ◽

Infectious Diseases ◽

Multidisciplinary Approach ◽

Preliminary Assessment ◽

Epidemiological Evidence ◽

Wide Range ◽

Human Coronaviruses ◽

Induced Changes ◽

And Behavior ◽

Timing Phase

Not 1 year has passed since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19). Since its emergence, great uncertainty has surrounded the potential for COVID-19 to establish as a seasonally recurrent disease. Many infectious diseases, including endemic human coronaviruses, vary across the year. They show a wide range of seasonal waveforms, timing (phase), and amplitudes, which differ depending on the geographical region. Drivers of such patterns are predominantly studied from an epidemiological perspective with a focus on weather and behavior, but complementary insights emerge from physiological studies of seasonality in animals, including humans. Thus, we take a multidisciplinary approach to integrate knowledge from usually distinct fields. First, we review epidemiological evidence of environmental and behavioral drivers of infectious disease seasonality. Subsequently, we take a chronobiological perspective and discuss within-host changes that may affect susceptibility, morbidity, and mortality from infectious diseases. Based on photoperiodic, circannual, and comparative human data, we not only identify promising future avenues but also highlight the need for further studies in animal models. Our preliminary assessment is that host immune seasonality warrants evaluation alongside weather and human behavior as factors that may contribute to COVID-19 seasonality, and that the relative importance of these drivers requires further investigation. A major challenge to predicting seasonality of infectious diseases are rapid, human-induced changes in the hitherto predictable seasonality of our planet, whose influence we review in a final outlook section. We conclude that a proactive multidisciplinary approach is warranted to predict, mitigate, and prevent seasonal infectious diseases in our complex, changing human-earth system.

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Waning antibody responses in COVID-19: what can we learn from the analysis of other coronaviruses?

Infection ◽

10.1007/s15010-021-01664-z ◽

2021 ◽

Author(s):

Ali Hamady ◽

JinJu Lee ◽

Zuzanna A. Loboda

Keyword(s):

Cross Reactivity ◽

Antibody Responses ◽

The Novel ◽

Incidence And Mortality ◽

Antibody Titres ◽

Human Coronaviruses ◽

Public Health Strategies ◽

Antibody Dynamics

Abstract Objectives The coronavirus disease 2019 (COVID-19), caused by the novel betacoronavirus severe acute respiratory syndrome 2 (SARS-CoV-2), was declared a pandemic in March 2020. Due to the continuing surge in incidence and mortality globally, determining whether protective, long-term immunity develops after initial infection or vaccination has become critical. Methods/Results In this narrative review, we evaluate the latest understanding of antibody-mediated immunity to SARS-CoV-2 and to other coronaviruses (SARS-CoV, Middle East respiratory syndrome coronavirus and the four endemic human coronaviruses) in order to predict the consequences of antibody waning on long-term immunity against SARS-CoV-2. We summarise their antibody dynamics, including the potential effects of cross-reactivity and antibody waning on vaccination and other public health strategies. At present, based on our comparison with other coronaviruses we estimate that natural antibody-mediated protection for SARS-CoV-2 is likely to last for 1–2 years and therefore, if vaccine-induced antibodies follow a similar course, booster doses may be required. However, other factors such as memory B- and T-cells and new viral strains will also affect the duration of both natural and vaccine-mediated immunity. Conclusion Overall, antibody titres required for protection are yet to be established and inaccuracies of serological methods may be affecting this. We expect that with standardisation of serological testing and studies with longer follow-up, the implications of antibody waning will become clearer.

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Persistent COVID-19 Symptoms Minimally Impact the Development of SARS-CoV-2-Specific T Cell Immunity

Viruses ◽

10.3390/v13050916 ◽

2021 ◽

Vol 13 (5) ◽

pp. 916

Author(s):

Hengsheng Fang ◽

Adam D. Wegman ◽

Kianna Ripich ◽

Heather Friberg ◽

Jeffrey R. Currier ◽

...

Keyword(s):

Cellular Immunity ◽

Viral Infections ◽

T Cell Immunity ◽

N Protein ◽

Cell Immunity ◽

Public Health Challenge ◽

Human Coronaviruses ◽

Cellular Immune ◽

Persistent Viral Infections ◽

Insight Into

SARS-CoV-2 represents an unprecedented public health challenge. While the majority of SARS-CoV-2-infected individuals with mild-to-moderate COVID-19 resolve their infection with few complications, some individuals experience prolonged symptoms lasting for weeks after initial diagnosis. Persistent viral infections are commonly accompanied by immunologic dysregulation, but it is unclear if persistent COVID-19 impacts the development of virus-specific cellular immunity. To this end, we analyzed SARS-CoV-2-specific cellular immunity in convalescent COVID-19 patients who experienced eight days or fewer of COVID-19 symptoms or symptoms persisting for 18 days or more. We observed that persistent COVID-19 symptoms were not associated with the development of an overtly dysregulated cellular immune response. Furthermore, we observed that reactivity against the N protein from SARS-CoV-2 correlates with the amount of reactivity against the seasonal human coronaviruses 229E and NL63. These results provide insight into the processes that regulate the development of cellular immunity against SARS-CoV-2 and related human coronaviruses.

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Comparative analysis of human coronaviruses focusing on nucleotide variability and synonymous codon usage patterns

Genomics ◽

10.1016/j.ygeno.2021.05.008 ◽

2021 ◽

Author(s):

Jayanta Kumar Das ◽

Swarup Roy

Keyword(s):

Comparative Analysis ◽

Codon Usage ◽

Synonymous Codon ◽

Synonymous Codon Usage ◽

Nucleotide Variability ◽

Usage Patterns ◽

Human Coronaviruses

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Repurposing CFDA-approved drug carrimycin as an antiviral agent against human coronaviruses, including the currently pandemic SARS-CoV-2

Acta Pharmaceutica Sinica B ◽

10.1016/j.apsb.2021.02.024 ◽

2021 ◽

Author(s):

Haiyan Yan ◽

Jing Sun ◽

Kun Wang ◽

Huiqiang Wang ◽

Shuo Wu ◽

...

Keyword(s):

Antiviral Agent ◽

Human Coronaviruses

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Circulating CD4 T cells elicited by endemic coronaviruses display vast disparities in abundance and functional potential linked to both antigen specificity and age

The Journal of Infectious Diseases ◽

10.1093/infdis/jiab076 ◽

2021 ◽

Author(s):

Katherine A Richards ◽

Maryah Glover ◽

Jeremy C Crawford ◽

Paul Thomas ◽

Chantelle White ◽

...

Keyword(s):

T Cells ◽

Cd4 T Cells ◽

Protective Immunity ◽

Granzyme B ◽

Antigen Specificity ◽

Functional Potential ◽

Membrane Envelope ◽

Ifn Γ ◽

Human Coronaviruses ◽

Repeated Infections

Abstract Repeated infections with endemic human coronaviruses are thought to reflect lack of long-lasting protective immunity. Here, we evaluate circulating human CD4 T cells collected prior to 2020 for reactivity towards hCoV spike proteins, probing for the ability to produce IFN-γ, IL-2 or granzyme B. We find robust reactivity to spike-derived epitopes, comparable to influenza, but highly variable abundance and functional potential across subjects, depending on age and viral antigen specificity. To explore the potential of these memory cells to be recruited in SARS-CoV-2 infection, we examined the same subjects for cross-reactive recognition of epitopes from SARS-CoV-2 nucleocapsid, membrane/envelope, and spike. The functional potential of these cross-reactive CD4 T cells was highly variable, with nucleocapsid-specific CD4 T cells, but not spike-reactive cells showing exceptionally high levels of granzyme production upon stimulation. These results are considered in light of recruitment of hCoV-reactive cells into responses of humans to SARS-CoV infections or vaccinations.

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