Host Response against SARS-CoV-2 Infection: Implications for Diagnosis, Treatment and Vaccine Development

Journal Name	Impact Factor	CiteScore	Launched Year	First Decision (median)	APC
Antibodies antibodies	-	0.9	2012	17.8 Days	1600 CHF	Submit
COVID covid	-	-	2021	16.5 Days	1000 CHF	Submit
Pathogens pathogens	4.531	3.5	2012	15.9 Days	2200 CHF	Submit
Vaccines vaccines	4.961	4.5	2013	17.3 Days	2200 CHF	Submit
Viruses viruses	5.818	6.6	2009	15.6 Days	2600 CHF	Submit

Open AccessReview

Implications of COVID-19 Pandemic on Pregnancy: Current Status and Controversies

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Grace C. Greenberg

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Nandini Vishwakarma

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Myna Prakash Tirupattur

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Hannah M. Sprague

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Laxmansa C. Katwa

COVID 2023, 3(6), 859-873; https://doi.org/10.3390/covid3060062 - 26 May 2023

Viewed by 426

Abstract

The COVID-19 pandemic unnerved the global population in 2019 and has continued to evolve ever since. Throughout this time, investigations concerning the health of the groups most susceptible to this virus, including the elderly, those with compromised immunity or chronic diseases, and pregnant [...] Read more.

The COVID-19 pandemic unnerved the global population in 2019 and has continued to evolve ever since. Throughout this time, investigations concerning the health of the groups most susceptible to this virus, including the elderly, those with compromised immunity or chronic diseases, and pregnant women, have taken place. Numerous articles have been formulated on the effects of COVID-19 infection on maternal, fetal, and neonatal health, but there are many controversies that still exist within the current literature. Even three years later, it is not fully understood how a maternal infection or vaccination of COVID-19 can impact pregnancy and the fetus, and these topics require further investigation and conclusive results. The aim of this article is to explain the risks for a mother and the neonate, during and after pregnancy, with the emergence of the COVID-19 pandemic. Additionally, this report presents the current state of the literature on whether vaccination during pregnancy is more beneficial or harmful. Finally, this review examines studies regarding the exacerbation of the effects of COVID-19 on pregnancies in various organ systems, particularly the cardiovascular system, in relevance to pre-existing and emerging conditions and the ethnicity of the mother. Full article

(This article belongs to the Topic Host Response against SARS-CoV-2 Infection: Implications for Diagnosis, Treatment and Vaccine Development)

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Open AccessArticle

Both Feline Coronavirus Serotypes 1 and 2 Infected Domestic Cats Develop Cross-Reactive Antibodies to SARS-CoV-2 Receptor Binding Domain: Its Implication to Pan-CoV Vaccine Development

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Subhashinie Kariyawasam

Viruses 2023, 15(4), 914; https://doi.org/10.3390/v15040914 - 31 Mar 2023

Cited by 1 | Viewed by 1444

Abstract

The current study was initiated when our specific-pathogen-free laboratory toms developed unexpectedly high levels of cross-reactive antibodies to human SARS-CoV-2 (SCoV2) receptor binding domain (RBD) upon mating with feline coronavirus (FCoV)-positive queens. Multi-sequence alignment analyses of SCoV2 Wuhan RBD and four strains each [...] Read more.

The current study was initiated when our specific-pathogen-free laboratory toms developed unexpectedly high levels of cross-reactive antibodies to human SARS-CoV-2 (SCoV2) receptor binding domain (RBD) upon mating with feline coronavirus (FCoV)-positive queens. Multi-sequence alignment analyses of SCoV2 Wuhan RBD and four strains each from FCoV serotypes 1 and 2 (FCoV1 and FCoV2) demonstrated an amino acid sequence identity of 11.5% and a similarity of 31.8% with FCoV1 RBD (12.2% identity and 36.5% similarity for FCoV2 RBD). The sera from toms and queens cross-reacted with SCoV2 RBD and reacted with FCoV1 RBD and FCoV2 spike-2, nucleocapsid, and membrane proteins, but not with FCoV2 RBD. Thus, the queens and toms were infected with FCoV1. Additionally, the plasma from six FCoV2-inoculated cats reacted with FCoV2 and SCoV2 RBDs, but not with FCoV1 RBD. Hence, the sera from both FCoV1-infected cats and FCoV2-infected cats developed cross-reactive antibodies to SCoV2 RBD. Furthermore, eight group-housed laboratory cats had a range of serum cross-reactivity to SCoV2 RBD even 15 months later. Such cross-reactivity was also observed in FCoV1-positive group-housed pet cats. The SCoV2 RBD at a high non-toxic dose and FCoV2 RBD at a 60–400-fold lower dose blocked the in vitro FCoV2 infection, demonstrating their close structural conformations essential as vaccine immunogens. Remarkably, such cross-reactivity was also detected by the peripheral blood mononuclear cells of FCoV1-infected cats. The broad cross-reactivity between human and feline RBDs provides essential insights into developing a pan-CoV vaccine. Full article

(This article belongs to the Topic Host Response against SARS-CoV-2 Infection: Implications for Diagnosis, Treatment and Vaccine Development)

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Open AccessSystematic Review

Impact of COVID-19 Vaccination on Pregnant Women

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Narayanaiah Cheedarla

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Esaki M. Shankar

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Ramachandran Vignesh

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Vijayakumar Velu

Pathogens 2023, 12(3), 431; https://doi.org/10.3390/pathogens12030431 - 09 Mar 2023

Viewed by 1345

Abstract

In light of the COVID-19 pandemic, researchers across the world hastened to develop vaccines that would aid in bolstering herd immunity. Utilizing mRNA coding and viral vector technology, the currently approved vaccines were required to undergo extensive testing to confirm their safety for [...] Read more.

In light of the COVID-19 pandemic, researchers across the world hastened to develop vaccines that would aid in bolstering herd immunity. Utilizing mRNA coding and viral vector technology, the currently approved vaccines were required to undergo extensive testing to confirm their safety for mass usage in the general population. However, clinical trials failed to test the safety and efficacy of the COVID-19 vaccines in groups with weakened immune systems, especially pregnant women. Lack of information on the effects of vaccinations in pregnancy and the safety of fetuses are among the topmost reasons preventing pregnant women from receiving immunization. Thus, the lack of data examining the effects of COVID-19 vaccinations on pregnant women must be addressed. This review focused on the safety and efficacy of the approved COVID-19 vaccinations in pregnancy and their impact on both maternal and fetal immune responses. For that, we took the approach of combined systematic review/meta-analysis and compiled the available data from the original literature from PubMed, Web of Science, EMBASE and Medline databases. All articles analyzed presented no adverse effects of vaccination in pregnancy, with varying conclusions on the degree of effectiveness. The majority of the findings described robust immune responses in vaccinated pregnant women, successful transplacental antibody transfer, and implications for neonatal immunity. Hence, findings from the cumulative data available can be helpful in achieving COVID-19 herd immunization, including pregnant women. Full article

(This article belongs to the Topic Host Response against SARS-CoV-2 Infection: Implications for Diagnosis, Treatment and Vaccine Development)

Open AccessArticle

Human Genome Polymorphisms and Computational Intelligence Approach Revealed a Complex Genomic Signature for COVID-19 Severity in Brazilian Patients

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André Filipe Pastor

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Cássia Docena

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Antônio Mauro Rezende

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Flávio Rosendo da Silva Oliveira

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Marília de Albuquerque Sena

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Clarice Neuenschwander Lins de Morais

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Cristiane Campello Bresani-Salvi

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Luydson Richardson Silva Vasconcelos

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Kennya Danielle Campelo Valença

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Carolline de Araújo Mariz

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Carlos Brito

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Cláudio Duarte Fonseca

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Cynthia Braga

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Christian Robson de Souza Reis

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Ernesto Torres de Azevedo Marques

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Bartolomeu Acioli-Santos

Viruses 2023, 15(3), 645; https://doi.org/10.3390/v15030645 - 28 Feb 2023

Viewed by 814

Abstract

We present a genome polymorphisms/machine learning approach for severe COVID-19 prognosis. Ninety-six Brazilian severe COVID-19 patients and controls were genotyped for 296 innate immunity loci. Our model used a feature selection algorithm, namely recursive feature elimination coupled with a support vector machine, to [...] Read more.

We present a genome polymorphisms/machine learning approach for severe COVID-19 prognosis. Ninety-six Brazilian severe COVID-19 patients and controls were genotyped for 296 innate immunity loci. Our model used a feature selection algorithm, namely recursive feature elimination coupled with a support vector machine, to find the optimal loci classification subset, followed by a support vector machine with the linear kernel (SVM-LK) to classify patients into the severe COVID-19 group. The best features that were selected by the SVM-RFE method included 12 SNPs in 12 genes: PD-L1, PD-L2, IL10RA, JAK2, STAT1, IFIT1, IFIH1, DC-SIGNR, IFNB1, IRAK4, IRF1, and IL10. During the COVID-19 prognosis step by SVM-LK, the metrics were: 85% accuracy, 80% sensitivity, and 90% specificity. In comparison, univariate analysis under the 12 selected SNPs showed some highlights for individual variant alleles that represented risk (PD-L1 and IFIT1) or protection (JAK2 and IFIH1). Variant genotypes carrying risk effects were represented by PD-L2 and IFIT1 genes. The proposed complex classification method can be used to identify individuals who are at a high risk of developing severe COVID-19 outcomes even in uninfected conditions, which is a disruptive concept in COVID-19 prognosis. Our results suggest that the genetic context is an important factor in the development of severe COVID-19. Full article

(This article belongs to the Topic Host Response against SARS-CoV-2 Infection: Implications for Diagnosis, Treatment and Vaccine Development)

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Open AccessArticle

Assessment of the Biological Impact of SARS-CoV-2 Genetic Variation Using an Authentic Virus Neutralisation Assay with Convalescent Plasma, Vaccinee Sera, and Standard Reagents

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Viruses 2023, 15(3), 633; https://doi.org/10.3390/v15030633 - 25 Feb 2023

Cited by 1 | Viewed by 1026

Abstract

In the summer of 2020, it became clear that the genetic composition of SARS-CoV-2 was changing rapidly. This was highlighted by the rapid emergence of the D614G mutation at that time. In the autumn of 2020, the project entitled “Agility” was initiated with [...] Read more.

In the summer of 2020, it became clear that the genetic composition of SARS-CoV-2 was changing rapidly. This was highlighted by the rapid emergence of the D614G mutation at that time. In the autumn of 2020, the project entitled “Agility” was initiated with funding from the Coalition for Epidemic Preparedness Innovations (CEPI) to assess new variants of SARS-CoV-2. The project was designed to reach out and intercept swabs containing live variant viruses in order to generate highly characterised master and working stocks, and to assess the biological consequences of the rapid genetic changes using both in vitro and in vivo approaches. Since November 2020, a total of 21 variants have been acquired and tested against either a panel of convalescent sera from early in the pandemic, and/or a panel of plasma from triple-vaccinated participants. A pattern of continuous evolution of SARS-CoV-2 has been revealed. Sequential characterisation of the most globally significant variants available to us, generated in real-time, indicated that the most recent Omicron variants appear to have evolved in a manner that avoids immunological recognition by convalescent plasma from the era of the ancestral virus when analysed in an authentic virus neutralisation assay. Full article

(This article belongs to the Topic Host Response against SARS-CoV-2 Infection: Implications for Diagnosis, Treatment and Vaccine Development)

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Open AccessReview

Employing T-Cell Memory to Effectively Target SARS-CoV-2

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Zaw Htet Tun

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Nang Thinn Thinn Htike

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Chaw Kyi-Tha-Thu

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Wing-Hin Lee

Pathogens 2023, 12(2), 301; https://doi.org/10.3390/pathogens12020301 - 11 Feb 2023

Viewed by 1021

Abstract

Well-trained T-cell immunity is needed for early viral containment, especially with the help of an ideal vaccine. Although most severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected convalescent cases have recovered with the generation of virus-specific memory T cells, some cases have encountered T-cell [...] Read more.

Well-trained T-cell immunity is needed for early viral containment, especially with the help of an ideal vaccine. Although most severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected convalescent cases have recovered with the generation of virus-specific memory T cells, some cases have encountered T-cell abnormalities. The emergence of several mutant strains has even threatened the effectiveness of the T-cell immunity that was established with the first-generation vaccines. Currently, the development of next-generation vaccines involves trying several approaches to educate T-cell memory to trigger a broad and fast response that targets several viral proteins. As the shaping of T-cell immunity in its fast and efficient form becomes important, this review discusses several interesting vaccine approaches to effectively employ T-cell memory for efficient viral containment. In addition, some essential facts and future possible consequences of using current vaccines are also highlighted. Full article

(This article belongs to the Topic Host Response against SARS-CoV-2 Infection: Implications for Diagnosis, Treatment and Vaccine Development)

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Open AccessArticle

SARS-CoV-2 Omicron BA.4/BA.5 Mutations in Spike Leading to T Cell Escape in Recently Vaccinated Individuals

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Cécile A. C. M. van Els

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Patricia Kaaijk

Viruses 2023, 15(1), 101; https://doi.org/10.3390/v15010101 - 29 Dec 2022

Cited by 2 | Viewed by 2310

Abstract

SARS-CoV-2 Omicron (B.1.1.529) lineages rapidly became dominant in various countries reflecting its enhanced transmissibility and ability to escape neutralizing antibodies. Although T cells induced by ancestral SARS-CoV-2-based vaccines also recognize Omicron variants, we showed in our previous study that there was a marked [...] Read more.

SARS-CoV-2 Omicron (B.1.1.529) lineages rapidly became dominant in various countries reflecting its enhanced transmissibility and ability to escape neutralizing antibodies. Although T cells induced by ancestral SARS-CoV-2-based vaccines also recognize Omicron variants, we showed in our previous study that there was a marked loss of T cell cross-reactivity to spike epitopes harboring Omicron BA.1 mutations. The emerging BA.4/BA.5 subvariants carry other spike mutations than the BA.1 variant. The present study aims to investigate the impact of BA.4/BA.5 spike mutations on T cell cross-reactivity at the epitope level. Here, we focused on universal T-helper epitopes predicted to be presented by multiple common HLA class II molecules for broad population coverage. Fifteen universal T-helper epitopes of ancestral spike, which contain mutations in the Omicron BA.4/BA.5 variants, were identified utilizing a bioinformatic tool. T cells isolated from 10 subjects, who were recently vaccinated with mRNA-based BNT162b2, were tested for functional cross-reactivity between epitopes of ancestral SARS-CoV-2 spike and the Omicron BA.4/BA.5 spike counterparts. Reduced T cell cross-reactivity in one or more vaccinees was observed against 87% of the tested 15 non-conserved CD4⁺ T cell epitopes. These results should be considered for vaccine boosting strategies to protect against Omicron BA.4/BA.5 and future SARS-CoV-2 variants. Full article

(This article belongs to the Topic Host Response against SARS-CoV-2 Infection: Implications for Diagnosis, Treatment and Vaccine Development)

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Open AccessArticle

Kinetics of Immune Subsets in COVID-19 Patients Treated with Corticosteroids

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Apostolos Georgios Pappas

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Anna-Louiza Chaliasou

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Andreas Panagopoulos

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Konstantina Dede

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Stavroula Daskalopoulou

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Alexandra Tsirogianni

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Ioannis Kalomenidis

Viruses 2023, 15(1), 51; https://doi.org/10.3390/v15010051 - 24 Dec 2022

Cited by 1 | Viewed by 1237

Abstract

Rationale: Changes in anti-SARS-CoV-2 defense immune subsets in patients treated with dexamethasone (DXM) for severe COVID-19 and their relation to disease outcomes are poorly understood. Methods: Blood-lymphocyte subsets of 110 hospitalized COVID-19 patients were prospectively examined. A first sample was taken at enrollment [...] Read more.

Rationale: Changes in anti-SARS-CoV-2 defense immune subsets in patients treated with dexamethasone (DXM) for severe COVID-19 and their relation to disease outcomes are poorly understood. Methods: Blood-lymphocyte subsets of 110 hospitalized COVID-19 patients were prospectively examined. A first sample was taken at enrollment and a second one 7–10 days later. Total B-, T-lymphocytes, CD4+, CD8+, T-regulatory (Treg), Natural-Killer (NK) and NK T-cells were counted using flow cytometry. Results: At enrollment, patients with respiratory failure, characterized by DXM failure (intubation/death) or DXM success (hospital discharge) exhibited significantly fewer CD3+, CD4+ and CD8+ cells and B-lymphocytes compared to the control group (no respiratory failure/no DXM). At the time of treatment completion, the DXM-failure group exhibited significantly fewer CD3+, CD4+ and CD8+ cells, memory CD4+ and CD8+ T-lymphocytes, compared to the control and the DXM-success groups and fewer activated CD4+ T-lymphocytes, Tregs and NK cells compared to the control group. At the time of treatment completion, the number of all investigated lymphocyte subsets increased in the DXM-success group and was similar to those of the control group. NK cells significantly decreased over time in the DXM-failure group. Conclusion: The lymphocyte kinetics differ between DXM-treated and control COVID-19 patients and are associated with clinical outcomes. Full article

(This article belongs to the Topic Host Response against SARS-CoV-2 Infection: Implications for Diagnosis, Treatment and Vaccine Development)

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Open AccessArticle

Antibodies Induced by Homologous or Heterologous Inactivated (CoronaVac/BBIBP-CorV) and Recombinant Protein Subunit Vaccines (ZF2001) Dramatically Enhanced Inhibitory Abilities against B.1.351, B.1.617.2, and B.1.1.529 Variants

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Vaccines 2022, 10(12), 2110; https://doi.org/10.3390/vaccines10122110 - 09 Dec 2022

Cited by 2 | Viewed by 785

Abstract

Safe and effective vaccines for Corona Virus Disease 2019 (COVID-19) can prevent the virus from infecting human populations and treat patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this study, we discuss the inhibitory abilities of primary and booster vaccine-induced [...] Read more.

Safe and effective vaccines for Corona Virus Disease 2019 (COVID-19) can prevent the virus from infecting human populations and treat patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this study, we discuss the inhibitory abilities of primary and booster vaccine-induced antibodies inhibitory ability toward the SARS-CoV-2 wild-type strain, as well as B.1.1.7, B.1.351, P.1, B.1.617.2, and B.1.1.529. We confirmed these antibodies had the strongest inhibitory effects on the wild-type strain and cross-inhibition activities against other mutant strains after two inactivated vaccine doses. However, the B.1.351, B.1.617.2 and B.1.1.529 mutants exhibit antibody resistance in the vaccine serum. Antibodies induced by homologous inactivated vaccines (n = 92) presented more effective inhibition against tested SARS-CoV-2 strains (p < 0.0001), especially B.1.351, B.1.617.2, and B.1.1.529 mutant strains, which had strong immune escape characteristics. In addition, a heterologous booster vaccination (n = 50) of a protein subunit vaccine ZifiVax (ZF2001) significantly restored humoral immune responses and even showed an increasing response against wild-type, B.1.351, B.1.617.2, and B.1.1.529 than homologous inactivated vaccines. Our analysis of the humoral immune response elicited by the different vaccine regimens, including inhibiting antibodies, indicated that a booster, whether homologous or heterologous, could be essential for achieving greater efficacy against SARS-CoV-2. Full article

(This article belongs to the Topic Host Response against SARS-CoV-2 Infection: Implications for Diagnosis, Treatment and Vaccine Development)

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Open AccessCommunication

Antibodies to Commonly Circulating Viral Pathogens Modulate Serological Response to Severe Acute Respiratory Syndrome Coronavirus 2 Infection

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Mohammad Zahirul Islam

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Dewan Md Emdadul Hoque

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Shehlina Ahmed

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Rubhana Raqib

COVID 2022, 2(12), 1625-1634; https://doi.org/10.3390/covid2120117 - 23 Nov 2022

Viewed by 898

Abstract

The purpose of this study was to determine the seropositivity of circulating viral pathogens and their association with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seropositivity. In a cross-sectional design, inhabitants (aged 10–60 years) of the slum and surrounding non-slum areas of Dhaka [...] Read more.

The purpose of this study was to determine the seropositivity of circulating viral pathogens and their association with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seropositivity. In a cross-sectional design, inhabitants (aged 10–60 years) of the slum and surrounding non-slum areas of Dhaka and Chattogram Metropolitan cities in Bangladesh were enrolled from October 2020 to February 2021. Antibodies to SARS-CoV-2, influenza B, parainfluenza, respiratory syncytial virus (RSV), human coronavirus HKU1 (HCoV-HKU1), dengue and chikungunya viruses were determined in plasma. The association of SARS-CoV-2 seropositivity with seropositivity to other viruses was assessed using the multi-variate logistic regression model. Seroprevalence of SARS-CoV-2, influenza B, RSV, dengue, chikungunya, HCoV-HKU1 and the parainfluenza virus were 68.3%, 98%, 50.0%, 16.5%, 15.5%, 3.36% and 0.0%, respectively. Individuals seropositive for RSV had lower odds (OR = 0.60; 95% CI= 0.49, 0.73) of SARS-CoV-2 seropositivity compared to RSV-seronegative individuals. Conversely, higher odds of SARS-CoV-2 seropositivity were observed in participants seropositive for dengue (OR= 1.73; 95% CI = 1.14, 2.66, only in slum) or chikungunya (OR = 1.48; 95% CI = 1.11, 1.95) compared to their seronegative counterparts. The study findings indicated that exposure to vector-borne virus dengue or chikungunya enhance, while antibodies to respiratory virus RSV decrease, the serological response to SARS-CoV-2. Full article

(This article belongs to the Topic Host Response against SARS-CoV-2 Infection: Implications for Diagnosis, Treatment and Vaccine Development)

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Open AccessArticle

Expression and Purification of Recombinant SARS-CoV-2 Accessory Protein ORF7a and Functional Analysis of Its Role in Up-Regulating Cytokine Production

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Dan Chen

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Zhenhua Zheng

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Zhenggang Han

COVID 2022, 2(10), 1449-1459; https://doi.org/10.3390/covid2100104 - 12 Oct 2022

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Abstract

The severity of coronavirus disease 2019 is closely linked to dysregulated immune responses. The search for viral proteins associated with immune regulation in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical to reveal the pathogenicity of the virus. In this study, accessory [...] Read more.

The severity of coronavirus disease 2019 is closely linked to dysregulated immune responses. The search for viral proteins associated with immune regulation in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical to reveal the pathogenicity of the virus. In this study, accessory proteins ORF7a (referred to as ORF7a-1 and ORF7a-2, respectively) from two SARS-related coronaviruses, severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2, were produced through the denaturing and refolding of inclusion body proteins. The recombinant protein was incubated with alveolar epithelial cells, and the transcription and expression levels of major cytokines were determined by reverse transcription-quantitative PCR and enzyme-linked immunosorbent assay. SARS-related coronavirus ORF7a can up-regulate the transcription and expression of interleukin-6, C-C motif chemokine ligand 8, interferon α, and interferon β. The results also indicated that the two highly conserved ORF7a had certain differences in promoting the transcription and expression of cytokines. The study showed that ORF7a is a virus-encoded immune regulator by alveolar epithelial cells that plays an important role in the pathogenicity of SARS-related coronaviruses. Full article

(This article belongs to the Topic Host Response against SARS-CoV-2 Infection: Implications for Diagnosis, Treatment and Vaccine Development)

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Open AccessArticle

In Vitro and In Vivo Characterization of a Broadly Neutralizing Anti-SARS-CoV-2 Antibody Isolated from a Semi-Immune Phage Display Library

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Edith González-González

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Gregorio Carballo-Uicab

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Juana Salinas-Trujano

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María I. Cortés-Paniagua

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Said Vázquez-Leyva

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Luis Vallejo-Castillo

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Ivette Mendoza-Salazar

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Keyla Gómez-Castellano

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Sonia M. Pérez-Tapia

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Juan C. Almagro

Antibodies 2022, 11(3), 57; https://doi.org/10.3390/antib11030057 - 06 Sep 2022

Cited by 2 | Viewed by 1779

Abstract

Neutralizing antibodies targeting the receptor-binding domain (RBD) of SARS-CoV-2 are among the most promising strategies to prevent and/or treat COVID-19. However, as SARS-CoV-2 has evolved into new variants, most of the neutralizing antibodies authorized by the US FDA and/or EMA to treat COVID-19 [...] Read more.

Neutralizing antibodies targeting the receptor-binding domain (RBD) of SARS-CoV-2 are among the most promising strategies to prevent and/or treat COVID-19. However, as SARS-CoV-2 has evolved into new variants, most of the neutralizing antibodies authorized by the US FDA and/or EMA to treat COVID-19 have shown reduced efficacy or have failed to neutralize the variants of concern (VOCs), particularly B.1.1.529 (Omicron). Previously, we reported the discovery and characterization of antibodies with high affinity for SARS-CoV-2 RBD Wuhan (WT), B.1.617.2 (Delta), and B.1.1.529 (Omicron) strains. One of the antibodies, called IgG-A7, also blocked the interaction of human angiotensin-converting enzyme 2 (hACE2) with the RBDs of the three strains, suggesting it may be a broadly SARS-CoV-2 neutralizing antibody. Herein, we show that IgG-A7 efficiently neutralizes all the three SARS-CoV-2 strains in plaque reduction neutralization tests (PRNTs). In addition, we demonstrate that IgG-A7 fully protects K18-hACE2 transgenic mice infected with SARS-CoV-2 WT. Taken together, our findings indicate that IgG-A7 could be a suitable candidate for development of antibody-based drugs to treat and/or prevent SARS-CoV-2 VOCs infection. Full article

(This article belongs to the Topic Host Response against SARS-CoV-2 Infection: Implications for Diagnosis, Treatment and Vaccine Development)

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Open AccessArticle

A Novel Single-Stranded RNA-Based Adjuvant Improves the Immunogenicity of the SARS-CoV-2 Recombinant Protein Vaccine

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Viruses 2022, 14(9), 1854; https://doi.org/10.3390/v14091854 - 24 Aug 2022

Cited by 1 | Viewed by 1279

Abstract

The research and development (R&D) of novel adjuvants is an effective measure for improving the immunogenicity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recombinant protein vaccine. Toward this end, we designed a novel single-stranded RNA-based adjuvant, L2, from the SARS-CoV-2 prototype [...] Read more.

The research and development (R&D) of novel adjuvants is an effective measure for improving the immunogenicity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recombinant protein vaccine. Toward this end, we designed a novel single-stranded RNA-based adjuvant, L2, from the SARS-CoV-2 prototype genome. L2 could initiate retinoic acid-inducible gene-I signaling pathways to effectively activate the innate immunity. ZF2001, an aluminum hydroxide (Al) adjuvanted SARS-CoV-2 recombinant receptor binding domain (RBD) subunit vaccine with emergency use authorization in China, was used for comparison. L2, with adjuvant compatibility with RBD, elevated the antibody response to a level more than that achieved with Al, CpG 7909, or poly(I:C) as adjuvants in mice. L2 plus Al with composite adjuvant compatibility with RBD markedly improved the immunogenicity of ZF2001; in particular, neutralizing antibody titers increased by about 44-fold for Omicron, and the combination also induced higher levels of antibodies than CpG 7909/poly(I:C) plus Al in mice. Moreover, L2 and L2 plus Al effectively improved the Th1 immune response, rather than the Th2 immune response. Taken together, L2, used as an adjuvant, enhanced the immune response of the SARS-CoV-2 recombinant RBD protein vaccine in mice. These findings should provide a basis for the R&D of novel RNA-based adjuvants. Full article

(This article belongs to the Topic Host Response against SARS-CoV-2 Infection: Implications for Diagnosis, Treatment and Vaccine Development)

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Open AccessBrief Report

Time-of-Day Variation in SARS-CoV-2 RNA Levels during the Second Wave of COVID-19

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Viruses 2022, 14(8), 1728; https://doi.org/10.3390/v14081728 - 05 Aug 2022

Cited by 1 | Viewed by 1322

Abstract

Circadian rhythms influence and coordinate an organism’s response to its environment and to invading pathogens. We studied the diurnal variation in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in nasal/throat swabs collected in late 2020 to spring 2021 in a population immunologically [...] Read more.

Circadian rhythms influence and coordinate an organism’s response to its environment and to invading pathogens. We studied the diurnal variation in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in nasal/throat swabs collected in late 2020 to spring 2021 in a population immunologically naïve to SARS-CoV-2 and prior to widespread vaccination. SARS-CoV-2 diagnostic PCR data from 1698 participants showed a significantly higher viral load in samples obtained in the afternoon, in males, and in hospitalised patients when linear mixed modelling was applied. This study illustrates the importance of recording sample collection times when measuring viral replication parameters in clinical and research studies. Full article

(This article belongs to the Topic Host Response against SARS-CoV-2 Infection: Implications for Diagnosis, Treatment and Vaccine Development)

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Open AccessArticle

DNA-Vaccine-Induced Immune Response Correlates with Lower Viral SARS-CoV-2 Titers in a Ferret Model

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Francisco J. Salguero

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Jemma Paterson

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Matteo Iannacone

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Raffaele De Francesco

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Luigi Aurisicchio

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Fabio Palombo

Vaccines 2022, 10(8), 1178; https://doi.org/10.3390/vaccines10081178 - 25 Jul 2022

Cited by 3 | Viewed by 1583

Abstract

The COVID-19 pandemic is entering a new era with the approval of many SARS-CoV-2 vaccines. In spite of the restoration of an almost normal way of life thanks to the immune protection elicited by these innovative vaccines, we are still facing high viral [...] Read more.

The COVID-19 pandemic is entering a new era with the approval of many SARS-CoV-2 vaccines. In spite of the restoration of an almost normal way of life thanks to the immune protection elicited by these innovative vaccines, we are still facing high viral circulation, with a significant number of deaths. To further explore alternative vaccination platforms, we developed COVID-eVax—a genetic vaccine based on plasmid DNA encoding the RBD domain of the SARS-CoV-2 spike protein. Here, we describe the correlation between immune responses and the evolution of viral infection in ferrets infected with the live virus. We demonstrate COVID-eVax immunogenicity as means of antibody response and, above all, a significant T-cell response, thus proving the critical role of T-cell immunity, in addition to the neutralizing antibody activity, in controlling viral spread. Full article

(This article belongs to the Topic Host Response against SARS-CoV-2 Infection: Implications for Diagnosis, Treatment and Vaccine Development)

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Host Response against SARS-CoV-2 Infection: Implications for Diagnosis, Treatment and Vaccine Development

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