scholarly journals Insights into COVID-19 Vaccine Development Based on Immunogenic Structural Proteins of SARS-CoV-2, Host Immune Responses, and Herd Immunity

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 2949
Author(s):  
Jitendra Kumar Chaudhary ◽  
Rohitash Yadav ◽  
Pankaj Kumar Chaudhary ◽  
Anurag Maurya ◽  
Nimita Kant ◽  
...  
Keyword(s):  
Immune Responses ◽  
Vaccine Development ◽  
Herd Immunity ◽  
Economic Recession ◽  
Alveolar Epithelial Cells ◽  
Structural Proteins ◽  
Human Society ◽  
Prophylactic Measure ◽  
Alveolar Epithelial ◽  
Advantages And Disadvantages

The first quarter of the 21st century has remarkably been characterized by a multitude of challenges confronting human society as a whole in terms of several outbreaks of infectious viral diseases, such as the 2003 severe acute respiratory syndrome (SARS), China; the 2009 influenza H1N1, Mexico; the 2012 Middle East respiratory syndrome (MERS), Saudi Arabia; and the ongoing coronavirus disease 19 (COVID-19), China. COVID-19, caused by SARS-CoV-2, reportedly broke out in December 2019, Wuhan, the capital of China’s Hubei province, and continues unabated, leading to considerable devastation and death worldwide. The most common target organ of SARS-CoV-2 is the lungs, especially the bronchial and alveolar epithelial cells, culminating in acute respiratory distress syndrome (ARDS) in severe patients. Nevertheless, other tissues and organs are also known to be critically affected following infection, thereby complicating the overall aetiology and prognosis. Excluding H1N1, the SARS-CoV (also referred as SARS-CoV-1), MERS, and SARS-CoV-2 are collectively referred to as coronaviruses, and taxonomically placed under the realm Riboviria, order Nidovirales, suborder Cornidovirineae, family Coronaviridae, subfamily Orthocoronavirinae, genus Betacoronavirus, and subgenus Sarbecovirus. As of 23 September 2021, the ongoing SARS-CoV-2 pandemic has globally resulted in around 229 million and 4.7 million reported infections and deaths, respectively, apart from causing huge psychosomatic debilitation, academic loss, and deep economic recession. Such an unprecedented pandemic has compelled researchers, especially epidemiologists and immunologists, to search for SARS-CoV-2-associated potential immunogenic molecules to develop a vaccine as an immediate prophylactic measure. Amongst multiple structural and non-structural proteins, the homotrimeric spike (S) glycoprotein has been empirically found as the most suitable candidate for vaccine development owing to its immense immunogenic potential, which makes it capable of eliciting both humoral and cell-mediated immune responses. As a consequence, it has become possible to design appropriate, safe, and effective vaccines, apart from related therapeutic agents, to reduce both morbidity and mortality. As of 23 September 2021, four vaccines, namely, Comirnaty, COVID-19 vaccine Janssen, Spikevax, and Vaxzevria, have received the European Medicines Agency’s (EMA) approval, and around thirty are under the phase three clinical trial with emergency authorization by the vaccine-developing country-specific National Regulatory Authority (NRA). In addition, 100–150 vaccines are under various phases of pre-clinical and clinical trials. The mainstay of global vaccination is to introduce herd immunity, which would protect the majority of the population, including immunocompromised individuals, from infection and disease. Here, we primarily discuss category-wise vaccine development, their respective advantages and disadvantages, associated efficiency and potential safety aspects, antigenicity of SARS-CoV-2 structural proteins and immune responses to them along with the emergence of SARS-CoV-2 VOC, and the urgent need of achieving herd immunity to contain the pandemic.

Coronaviruses: A Scientist’s Race Against Time

2020 ◽  
Author(s):  
Saloni Chaurasia ◽  
Keyword(s):  
Healthcare Workers ◽  
Vaccine Development ◽  
Drug Repurposing ◽  
Alveolar Epithelial Cells ◽  
Contact Tracing ◽  
Medical Innovation ◽  
Alveolar Epithelial ◽  
Treatment And Prevention ◽  
Scientific World ◽  
Respiratory Droplets

As the clock ticks, more and more people are falling victim to COVID-19, and scientists are racing against time to find treatment and prevention strategies. But what’s stopping them? The answer comes from two primary problems. Firstly, coronaviruses (CoVs) are transmitted from person-to-person via respiratory droplets from an infected person’s coughs or sneezes, which makes them highly contagious (CDC, How COVID-19 Spreads, 2020). This can happen in minutes, and up to 25% of patients remain asymptomatic (Du, et al., 2020). This makes it difficult for healthcare workers and researchers to contain patients and establish contact tracing to isolate the infected population. Secondly, it is hard to target CoVs without damaging our cells. CoVs infect via spike protein, which binds to the ACE2 receptor located on the lung alveolar epithelial cells (Hoffmann, et al., 2020). Once they invade the cell, CoVs hijack the host cell’s mechanisms to replicate. Thus, it is hard to combat the virus without damaging the host cell. On the other hand, recent understanding of CoVs structure and mechanism of action enables the scientific world to create a cure or vaccine. The bad news is that these efforts will likely face the perennial hurdles of medical innovation and discovery, long timelines of clinical trials for drug repurposing, and vaccine development, sometimes fickle funding, and changing governmental priorities.

scholarly journals Type I Alveolar Epithelial Cells Mount Innate Immune Responses during Pneumococcal Pneumonia

2012 ◽  
Vol 189 (5) ◽  
pp. 2450-2459 ◽  
Author(s):  
Kazuko Yamamoto ◽  
Joseph D. Ferrari ◽  
Yuxia Cao ◽  
Maria I. Ramirez ◽  
Matthew R. Jones ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Immune Responses ◽  
Pneumococcal Pneumonia ◽  
Innate Immune ◽  
Alveolar Epithelial Cells ◽  
Type I ◽  
Innate Immune Responses ◽  
Alveolar Epithelial

scholarly journals Unconventional secretion of unglycosylated ORF8 is critical for the cytokine storm during SARS-CoV-2 infection

2021 ◽  
Author(s):  
Xiaoyuan Lin ◽  
Beibei Fu ◽  
Yan Xiong ◽  
Na Xing ◽  
Weiwei Xue ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Immune Responses ◽  
Secretory Protein ◽  
Alveolar Epithelial Cells ◽  
Reading Frame ◽  
Functional Roles ◽  
Alveolar Epithelial ◽  
Host Immune Responses ◽  
Unconventional Secretion ◽  
Delayed Mortality

AbstractCoronavirus disease 2019 is a respiratory infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Evidence on the pathogenesis of SARS-CoV-2 is accumulating rapidly. In addition to structural proteins such as Spike and Envelope, the functional roles of non-structural and accessory proteins in regulating viral life cycle and host immune responses remain to be understood. Here, we show that open reading frame 8 (ORF8) acts as messenger for inter-cellular communication between alveolar epithelial cells and macrophages during SARS-CoV-2 infection. Mechanistically, ORF8 is a secretory protein that can be secreted by infected epithelial cells via both conventional and unconventional secretory pathways. The unconventionally secreted ORF8 recognizes the IL17RA receptor of macrophages and induces cytokine release. However, conventionally secreted ORF8 cannot bind to IL17RA due to N-linked glycosylation. Furthermore, we found that Yip1 interacting factor homolog B (YIF1B) is a channel protein that translocates unglycosylated ORF8 into vesicles for unconventional secretion. Blocking the unconventional secretion of ORF8 via a YIF1B knockout in hACE2 mice attenuates inflammation and yields delayed mortality following SARS-CoV-2 challenge.

Innate Immune Responses Of Type I Alveolar Epithelial Cells During Pneumonia

2012 ◽  
Author(s):  
Kazuko Yamamoto ◽  
Joseph D. Ferrari ◽  
Maria I. Ramirez ◽  
Matthew R. Jones ◽  
Lee J. Quinton ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Immune Responses ◽  
Innate Immune ◽  
Alveolar Epithelial Cells ◽  
Type I ◽  
Innate Immune Responses ◽  
Alveolar Epithelial

scholarly journals Nasal alum-adjuvanted vaccine promotes IL-33 release from alveolar epithelial cells that elicits IgA production via type 2 immune responses

2021 ◽  
Vol 17 (8) ◽  
pp. e1009890
Author(s):  
Eita Sasaki ◽  
Hideki Asanuma ◽  
Haruka Momose ◽  
Keiko Furuhata ◽  
Takuo Mizukami ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Immune Responses ◽  
Mhc Class Ii ◽  
T Cell Activation ◽  
Cultured Cells ◽  
Alveolar Epithelial Cell ◽  
Lymphoid Cells ◽  
Alveolar Epithelial Cells ◽  
Alveolar Epithelial ◽  
Deficient Mice

Aluminum hydroxide salts (alum) have been added to inactivated vaccines as safe and effective adjuvants to increase the effectiveness of vaccination. However, the exact cell types and immunological factors that initiate mucosal immune responses to alum adjuvants are unclear. In this study, the mechanism of action of alum adjuvant in nasal vaccination was investigated. Alum has been shown to act as a powerful and unique adjuvant when added to a nasal influenza split vaccine in mice. Alum is cytotoxic in the alveoli and stimulates the release of damage-associated molecular patterns, such as dsDNA, interleukin (IL)-1α, and IL-33. We found that Ag-specific IgA antibody (Ab) production was markedly reduced in IL-33-deficient mice. However, no decrease was observed in Ag-specific IgA Ab production with DNase I treatment, and no decrease was observed in IL-1α/β or IL-6 production in IL-33-deficient mice. From the experimental results of primary cultured cells and immunofluorescence staining, although IL-1α was secreted by alveolar macrophage necroptosis, IL-33 release was observed in alveolar epithelial cell necroptosis but not in alveolar macrophages. Alum- or IL-33-dependent Ag uptake enhancement and elevation of OX40L expression were not observed. By stimulating the release of IL-33, alum induced Th2 immunity via IL-5 and IL-13 production in group 2 innate lymphoid cells (ILC2s) and increased MHC class II expression in antigen-presenting cells (APCs) in the lung. Our results suggest that IL-33 secretion by epithelial cell necroptosis initiates APC- and ILC2-mediated T cell activation, which is important for the enhancement of Ag-specific IgA Ab production by alum.

scholarly journals The Role of Alveolar Epithelial Cells in Initiating and Shaping Pulmonary Immune Responses: Communication between Innate and Adaptive Immune Systems

PLoS ONE ◽  
2012 ◽  
Vol 7 (2) ◽  
pp. e32125 ◽  
Author(s):  
Olga D. Chuquimia ◽  
Dagbjort H. Petursdottir ◽  
Muhammad J. Rahman ◽  
Katharina Hartl ◽  
Mahavir Singh ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Immune Responses ◽  
Alveolar Epithelial Cells ◽  
Immune Systems ◽  
Alveolar Epithelial ◽  
Adaptive Immune ◽  
Adaptive Immune Systems

scholarly journals Age-elevated prostaglandin E2 enhances mortality to influenza infection

2021 ◽  
Author(s):  
Judy Chen ◽  
Jane C. Deng ◽  
Rachel Zemans ◽  
Min Zhang ◽  
Marc Peters-Golden ◽  
...  
Keyword(s):  
Immune Responses ◽  
Influenza A ◽  
Bronchoalveolar Lavage Fluid ◽  
Influenza Infection ◽  
Lavage Fluid ◽  
Alveolar Epithelial Cells ◽  
Prostaglandin E ◽  
Type Ii ◽  
Aged Mice ◽  
Alveolar Epithelial

SummaryAging impairs the immune responses to influenza A virus (IAV), resulting in increased mortality to IAV infections in older adults. With aging, there is reduced number and impaired function of alveolar macrophages (AMs), cells critical for defense against IAV. However, factors within the aged lung that impair AMs are not fully known. Using a murine model of IAV infection, we observed that aging increased the level of prostaglandin E2 (PGE2) in the bronchoalveolar lavage fluid (BALF) of aged mice compared to young mice. Blockade of the PGE2 receptor EP2 in aged mice increased AM numbers and subsequently enhanced survival to IAV. Additionally, PGE2 impaired the mitochondrial health of AMs. We also identified senescent type II alveolar epithelial cells (AECs) as a source of the aged-associated PGE2 in the lung. Our results reveal a crosstalk between AECs and AMs, via PGE2, that compromises host defense to IAV infection with aging.

scholarly journals Host signaling and proteolytic pathways in the resolution or the exacerbation of coronavirus (CoV-2) infection in COVID-19 disease: what therapeutic targets?

2020 ◽  
Author(s):  
Jean-Michel SALLENAVE ◽  
Loic Guillot
Keyword(s):  
Immune Responses ◽  
Serine Proteases ◽  
Multiple Organ ◽  
Innate Immune ◽  
Alveolar Epithelial Cells ◽  
Innate Immune Responses ◽  
Dipeptidyl Peptidase 4 ◽  
Alveolar Epithelial ◽  
Enveloped Virus ◽  
Host Signaling

COVID-19 is caused by the Severe Acute Respiratory Syndrome (SARS) coronavirus (Cov)-2, an enveloped virus with a positive single-stranded RNA genome. Pandemic initial outbreak began in December 2019 and is threatening the health of the global community. In common with previous pandemics (Influenza H1N1, SARS-CoV-1) and the epidemics of Middle east respiratory syndrome (MERS)-CoV, CoVs target bronchial and alveolar epithelial cells. Virus proteins ligands (eg haemagglutinin or spike protein for Influenza and CoV, respectively) interact with cellular receptors such as (depending on the virus), either sialic acids, Dipeptidyl peptidase 4 (DPP4), or angiotensin-converting enzyme 2 (ACE2). Host proteases, eg cathepsins, furin, or members of the type II transmembrane serine proteases (TTSP) family such as Transmembrane protease serine 2 (TMPRSS2) are involved in virus entry by proteolytically activating virus ligands. Also involved are Toll Like Receptor (TLR) familly members which up-regulate anti-viral and pro-inflammatory mediators (interleukin (IL)-6 and IL-8...), through the activation of Nuclear Factor (NF)-kB. When these events (virus cellular entry and innate immune responses) are uncontrolled, a deleterious systemic response is sometimes encountered in infected patients, leading to the well described ‘cytokine storm’ and an ensuing multiple organ failure, promoted by a down-regulation of dendritic cells, macrophage and T cell function.We aim to describe how the lung and systemic host innate immune responses affect survival either positively, through down-regulating initial viral load, or negatively, by triggering uncontrolled inflammation. An emphasis will be put on host cellular signaling pathways and proteases involved, with a view on tackling these therapeutically.

scholarly journals Influenza induces IL-8 and GM-CSF secretion by human alveolar epithelial cells through HGF/c-Met and TGF-α/EGFR signaling

2015 ◽  
Vol 308 (11) ◽  
pp. L1178-L1188 ◽  
Author(s):  
Yoko Ito ◽  
Kelly Correll ◽  
Rachel L. Zemans ◽  
Christina C. Leslie ◽  
Robert C. Murphy ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epithelial Cells ◽  
Immune Responses ◽  
Influenza Infection ◽  
Innate Immune ◽  
Alveolar Epithelial Cells ◽  
Innate Immune Responses ◽  
Egfr Signaling ◽  
Alveolar Epithelial ◽  
Gm Csf

The most severe complication of influenza is viral pneumonia, which can lead to the acute respiratory distress syndrome. Alveolar epithelial cells (AECs) are the first cells that influenza virus encounters upon entering the alveolus. Infected epithelial cells produce cytokines that attract and activate neutrophils and macrophages, which in turn induce damage to the epithelial-endothelial barrier. Hepatocyte growth factor (HGF)/c-Met and transforming growth factor-α (TGF-α)/epidermal growth factor receptor (EGFR) are well known to regulate repair of damaged alveolar epithelium by stimulating cell migration and proliferation. Recently, TGF-α/EGFR signaling has also been shown to regulate innate immune responses in bronchial epithelial cells. However, little is known about whether HGF/c-Met signaling alters the innate immune responses and whether the innate immune responses in AECs are regulated by HGF/c-Met and TGF-α/EGFR. We hypothesized that HGF/c-Met and TGF-α/EGFR would regulate innate immune responses to influenza A virus infection in human AECs. We found that recombinant human HGF (rhHGF) and rhTGF-α stimulated primary human AECs to secrete IL-8 and granulocyte macrophage colony-stimulating factor (GM-CSF) strongly and IL-6 and monocyte chemotactic protein 1 moderately. Influenza infection stimulated the secretion of IL-8 and GM-CSF by AECs plated on rat-tail collagen through EGFR activation likely by TGF-α released from AECs and through c-Met activated by HGF secreted from lung fibroblasts. HGF secretion by fibroblasts was stimulated by AEC production of prostaglandin E2 during influenza infection. We conclude that HGF/c-Met and TGF-α/EGFR signaling enhances the innate immune responses by human AECs during influenza infections.

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