Research

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24 pages, 7869 KiB

Open AccessArticle

Expression of Toll-like Receptors on the Immune Cells in Patients with Common Variable Immune Deficiency after Different Schemes of Influenza Vaccination

by Aristitsa Mikhailovna Kostinova, Elena Alexandrovna Latysheva, Nelly Kimovna Akhmatova, Anna Egorovna Vlasenko, Svetlana Anatolyevna Skhodova, Ekaterina Alexandrovna Khromova, Andrey Viktorovich Linok, Arseniy Alexandrovich Poddubikov, Tatyana Vasilievna Latysheva and Mikhail Petrovich Kostinov

Viruses 2023, 15(10), 2091; https://doi.org/10.3390/v15102091 - 14 Oct 2023

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Abstract

Background: for the first time, the effect of one and two doses of adjuvanted influenza vaccines on toll-like receptors (TLRs) in patients with common variable immunodeficiency (CVID) was studied and compared (primary vaccination with one vs. two doses, primary vs. repeated vaccination). Materials [...] Read more.

Background: for the first time, the effect of one and two doses of adjuvanted influenza vaccines on toll-like receptors (TLRs) in patients with common variable immunodeficiency (CVID) was studied and compared (primary vaccination with one vs. two doses, primary vs. repeated vaccination). Materials and methods: Six patients received one dose of quadrivalent adjuvanted influenza vaccine during the 2018–2019 and 2019–2020 influenza seasons, and nine patients with CVID received two doses of trivalent inactivated influenza vaccine during 2019–2020. Expression of TLRs was measured by flow cytometry. Results: The expression of toll-like receptors in patients with CVID was noted both with repeated (annual) administration of the influenza vaccine and in most cases was accompanied by an increase in the proportion of granulocytes (TLR3 and TLR9), lymphocytes (TLR3 and TLR8), and monocytes (TLR3 and TLR9). When carried out for the first time as a simultaneous vaccination with two doses it was accompanied by an increase in the proportion of granulocytes, lymphocytes expressing TLR9, and on monocytes—TLR3 and TLR9. Conclusion: in CVID patients, the use of adjuvanted vaccines is promising, and research on the influence of the innate immunity and more effective regimens should be continued. Full article

(This article belongs to the Special Issue Efficacy, Safety, and Immunogenicity of Vaccines against Viruses: From Network Medicine to Clinical Experimentation)

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13 pages, 3733 KiB

Open AccessArticle

Assessment of Peste des Petits Ruminants Antibodies in Vaccinated Pregnant Ewes of Kazakh Breed Fine-Fleeced and Determination of the Decreasing Trend of Maternal Immunity in Their Lambs

by Zhanat Amanova, Sholpan Turyskeldy, Zhanat Kondybaeva, Zhanna Sametova, Abdurakhman Usembai, Aslan Kerimbayev and Yerbol Bulatov

Viruses 2023, 15(10), 2054; https://doi.org/10.3390/v15102054 - 06 Oct 2023

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Abstract

In this article, we first assessed peste des petits ruminants (PPR) antibodies in vaccinated pregnant ewes of Kazakh breed fine-fleeced immunized with the PPR vaccine and the duration of maternal immunity in their lambs. Ewes in the last trimester of pregnancy and gestation [...] Read more.

In this article, we first assessed peste des petits ruminants (PPR) antibodies in vaccinated pregnant ewes of Kazakh breed fine-fleeced immunized with the PPR vaccine and the duration of maternal immunity in their lambs. Ewes in the last trimester of pregnancy and gestation were immunized with a vaccine from the Nigeria 75/1 strain of the PPR virus (PPRV) produced by the Research Institute of Biological Safety Problems (RIBSP), Kazakhstan. Serum samples from lambs born from vaccinated and unvaccinated ewes were collected a week after birth and at intervals of 7 days for 18 weeks after birth. Serum samples collected from lambs were tested for PPR antibodies using competitive ELISA and virus neutralization test (VNT). Maternal antibodies (MAs) in lambs born from vaccinated ewes were detected for up to 18 weeks, with a tendency to decrease starting at week 14, and by the end of the experiment receded below the protective level (<1:8). In the blood serum of a 14-week-old lamb with MAs (1:8), post vaccination with a field dose (10³ TCID50) of the vaccine against PPR, the titers of protective antibodies against PPRV increased to 1:16 on day 14 post vaccination, and the lamb was protected from infection with the field PPRV. A lamb of the same age with MAs in the 1:8 titer was 100% protected from infection with the field PPRV. Therefore, it is recommended that lambs of the Kazakh fine-wool breed be immunized from the age of 14 weeks or older to avoid a period of susceptibility. Full article

(This article belongs to the Special Issue Efficacy, Safety, and Immunogenicity of Vaccines against Viruses: From Network Medicine to Clinical Experimentation)

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15 pages, 1975 KiB

Open AccessArticle

Stochastic Interventional Vaccine Efficacy and Principal Surrogate Analyses of Antibody Markers as Correlates of Protection against Symptomatic COVID-19 in the COVE mRNA-1273 Trial

by Ying Huang, Nima S. Hejazi, Bryan Blette, Lindsay N. Carpp, David Benkeser, David C. Montefiori, Adrian B. McDermott, Youyi Fong, Holly E. Janes, Weiping Deng, Honghong Zhou, Christopher R. Houchens, Karen Martins, Lakshmi Jayashankar, Britta Flach, Bob C. Lin, Sarah O’Connell, Charlene McDanal, Amanda Eaton, Marcella Sarzotti-Kelsoe, Yiwen Lu, Chenchen Yu, Avi Kenny, Marco Carone, Chuong Huynh, Jacqueline Miller, Hana M. El Sahly, Lindsey R. Baden, Lisa A. Jackson, Thomas B. Campbell, Jesse Clark, Michele P. Andrasik, James G. Kublin, Lawrence Corey, Kathleen M. Neuzil, Rolando Pajon, Dean Follmann, Ruben O. Donis, Richard A. Koup, Peter B. Gilbert, on behalf of the Immune Assays, Moderna, Inc., Coronavirus Vaccine Prevention Network (CoVPN)/Coronavirus Efficacy (COVE) and United States Government (USG)/CoVPN Biostatistics Teams Show full author list Hide full author list

Viruses 2023, 15(10), 2029; https://doi.org/10.3390/v15102029 - 29 Sep 2023

Cited by 3 | Viewed by 1581

Abstract

The COVE trial randomized participants to receive two doses of mRNA-1273 vaccine or placebo on Days 1 and 29 (D1, D29). Anti-SARS-CoV-2 Spike IgG binding antibodies (bAbs), anti-receptor binding domain IgG bAbs, 50% inhibitory dilution neutralizing antibody (nAb) titers, and 80% inhibitory dilution [...] Read more.

The COVE trial randomized participants to receive two doses of mRNA-1273 vaccine or placebo on Days 1 and 29 (D1, D29). Anti-SARS-CoV-2 Spike IgG binding antibodies (bAbs), anti-receptor binding domain IgG bAbs, 50% inhibitory dilution neutralizing antibody (nAb) titers, and 80% inhibitory dilution nAb titers were measured at D29 and D57. We assessed these markers as correlates of protection (CoPs) against COVID-19 using stochastic interventional vaccine efficacy (SVE) analysis and principal surrogate (PS) analysis, frameworks not used in our previous COVE immune correlates analyses. By SVE analysis, hypothetical shifts of the D57 Spike IgG distribution from a geometric mean concentration (GMC) of 2737 binding antibody units (BAU)/mL (estimated vaccine efficacy (VE): 92.9% (95% CI: 91.7%, 93.9%)) to 274 BAU/mL or to 27,368 BAU/mL resulted in an overall estimated VE of 84.2% (79.0%, 88.1%) and 97.6% (97.4%, 97.7%), respectively. By binary marker PS analysis of Low and High subgroups (cut-point: 2094 BAU/mL), the ignorance interval (IGI) and estimated uncertainty interval (EUI) for VE were [85%, 90%] and (78%, 93%) for Low compared to [95%, 96%] and (92%, 97%) for High. By continuous marker PS analysis, the IGI and 95% EUI for VE at the 2.5th percentile (519.4 BAU/mL) vs. at the 97.5th percentile (9262.9 BAU/mL) of D57 Spike IgG concentration were [92.6%, 93.4%] and (89.2%, 95.7%) vs. [94.3%, 94.6%] and (89.7%, 97.0%). Results were similar for other D29 and D57 markers. Thus, the SVE and PS analyses additionally support all four markers at both time points as CoPs. Full article

(This article belongs to the Special Issue Efficacy, Safety, and Immunogenicity of Vaccines against Viruses: From Network Medicine to Clinical Experimentation)

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17 pages, 1762 KiB

Open AccessArticle

Mucosal Application of a Low-Energy Electron Inactivated Respiratory Syncytial Virus Vaccine Shows Protective Efficacy in an Animal Model

by Valentina Eberlein, Mareike Ahrends, Lea Bayer, Julia Finkensieper, Joana Kira Besecke, Yaser Mansuroglu, Bastian Standfest, Franziska Lange, Simone Schopf, Martin Thoma, Jennifer Dressman, Christina Hesse, Sebastian Ulbert and Thomas Grunwald

Viruses 2023, 15(9), 1846; https://doi.org/10.3390/v15091846 - 30 Aug 2023

Cited by 1 | Viewed by 1248

Abstract

Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infections in the elderly and in children, associated with pediatric hospitalizations. Recently, first vaccines have been approved for people over 60 years of age applied by intramuscular injection. However, a [...] Read more.

Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infections in the elderly and in children, associated with pediatric hospitalizations. Recently, first vaccines have been approved for people over 60 years of age applied by intramuscular injection. However, a vaccination route via mucosal application holds great potential in the protection against respiratory pathogens like RSV. Mucosal vaccines induce local immune responses, resulting in a fast and efficient elimination of respiratory viruses after natural infection. Therefore, a low-energy electron irradiated RSV (LEEI-RSV) formulated with phosphatidylcholine-liposomes (PC-LEEI-RSV) was tested ex vivo in precision cut lung slices (PCLSs) for adverse effects. The immunogenicity and protective efficacy in vivo were analyzed in an RSV challenge model after intranasal vaccination using a homologous prime-boost immunization regimen. No side effects of PC-LEEI-RSV in PCLS and an efficient antibody induction in vivo could be observed. In contrast to unformulated LEEI-RSV, the mucosal vaccination of mice with PC formulated LEEI-RSV showed a statistically significant reduction in viral load after challenge. These results are a proof-of-principle for the use of LEEI-inactivated viruses formulated with liposomes to be administered intranasally to induce a mucosal immunity that could also be adapted for other respiratory viruses. Full article

(This article belongs to the Special Issue Efficacy, Safety, and Immunogenicity of Vaccines against Viruses: From Network Medicine to Clinical Experimentation)

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19 pages, 3092 KiB

Open AccessArticle

The Insertion of an Evolutionary Lost Four-Amino-Acid Cytoplasmic Tail Peptide into a Syncytin-1 Vaccine Increases T- and B-Cell Responses in Mice

by Isabella Skandorff, Jasmin Gille, Emeline Ragonnaud, Anne-Marie Andersson, Silke Schrödel, Christian Thirion, Ralf Wagner and Peter Johannes Holst

Viruses 2023, 15(8), 1686; https://doi.org/10.3390/v15081686 - 03 Aug 2023

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Abstract

Human endogenous retrovirus type W (HERV-W) is expressed in various cancers. We previously developed an adenovirus-vectored cancer vaccine targeting HERV-W by encoding an assembled HERV-W group-specific antigen sequence and the HERV-W envelope sequence Syncytin-1. Syncytin-1 is constitutively fusogenic and forms large multinucleated cell [...] Read more.

Human endogenous retrovirus type W (HERV-W) is expressed in various cancers. We previously developed an adenovirus-vectored cancer vaccine targeting HERV-W by encoding an assembled HERV-W group-specific antigen sequence and the HERV-W envelope sequence Syncytin-1. Syncytin-1 is constitutively fusogenic and forms large multinucleated cell fusions when overexpressed. Consequently, immunising humans with a vaccine encoding Syncytin-1 can lead to the formation of extensive syncytia, which is undesirable and poses a potential safety issue. Here, we show experiments in cell lines that restoring an evolutionary lost cleavage site of the fusion inhibitory R-peptide of Syncytin-1 inhibit cell fusion. Interestingly, this modification of the HERV-W vaccine’s fusogenicity increased the expression of the vaccine antigens in vitro. It also enhanced Syncytin-1-specific antibody responses and CD8⁺-mediated T-cell responses compared to the wildtype vaccine in vaccinated mice, with a notable enhancement in responses to subdominant T-cell epitopes but equal responses to dominant epitopes and similar rates of survival following a tumour challenge. The impairment of cell–cell fusion and the enhanced immunogenicity profile of this HERV-W vaccine strengthens the prospects of obtaining a meaningful immune response against HERV-W in patients with HERV-W-overexpressing cancers. Full article

(This article belongs to the Special Issue Efficacy, Safety, and Immunogenicity of Vaccines against Viruses: From Network Medicine to Clinical Experimentation)

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20 pages, 3644 KiB

Open AccessArticle

Effect of Pre-Treatment with a Recombinant Chicken Interleukin-17A on Vaccine Induced Immunity against a Very Virulent Marek’s Disease Virus

by Nitish Boodhoo, Ayumi Matsuyama-Kato, Sugandha Raj, Fatemeh Fazel, Myles St-Denis and Shayan Sharif

Viruses 2023, 15(8), 1633; https://doi.org/10.3390/v15081633 - 27 Jul 2023

Viewed by 994

Abstract

The host response to pathogenic microbes can lead to expression of interleukin (IL)-17, which has antimicrobial and anti-viral activity. However, relatively little is known about the basic biological role of chicken IL-17A against avian viruses, particularly against Marek’s disease virus (MDV). We demonstrate [...] Read more.

The host response to pathogenic microbes can lead to expression of interleukin (IL)-17, which has antimicrobial and anti-viral activity. However, relatively little is known about the basic biological role of chicken IL-17A against avian viruses, particularly against Marek’s disease virus (MDV). We demonstrate that, following MDV infection, upregulation of IL-17A mRNA and an increase in the frequency of IL-17A+ T cells in the spleen occur compared to control chickens. To elaborate on the role of chIL-17A in MD, the full-length chIL-17A coding sequence was cloned into a pCDNA3.1-V5/HIS TOPO plasmid. The effect of treatment with pcDNA:chIL-17A plasmid in combination with a vaccine (HVT) and very virulent(vv)MDV challenge or vvMDV infection was assessed. In combination with HVT vaccination, chickens that were inoculated with the pcDNA:chIL-17A plasmid had reduced tumor incidence compared to chickens that received the empty vector control or that were vaccinated only (66.6% in the HVT + empty vector group and 73.33% in HVT group versus 53.3% in the HVT + pcDNA:chIL-17A). Further analysis demonstrated that the chickens that received the HVT vaccine and/or plasmid expressing IL-17A had lower MDV-Meq transcripts in the spleen. In conclusion, chIL-17A can influence the immunity conferred by HVT vaccination against MDV infection in chickens. Full article

(This article belongs to the Special Issue Efficacy, Safety, and Immunogenicity of Vaccines against Viruses: From Network Medicine to Clinical Experimentation)

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16 pages, 3566 KiB

Open AccessArticle

ICP8-vhs- HSV-2 Vaccine Expressing B7 Costimulation Molecules Optimizes Safety and Efficacy against HSV-2 Infection in Mice

by Maria Korom, Hong Wang, Kaelin M. Bernier, Brian J. Geiss and Lynda A. Morrison

Viruses 2023, 15(7), 1570; https://doi.org/10.3390/v15071570 - 18 Jul 2023

Viewed by 1379

Abstract

Herpes simplex virus 2 (HSV-2) causes most sexually transmitted genital ulcerative disease. No effective prophylactic vaccine is currently available. Replication-defective (ICP8-) HSV stimulates immune responses in animals without producing progeny virus, making it potentially useful as a safe form of a live vaccine [...] Read more.

Herpes simplex virus 2 (HSV-2) causes most sexually transmitted genital ulcerative disease. No effective prophylactic vaccine is currently available. Replication-defective (ICP8-) HSV stimulates immune responses in animals without producing progeny virus, making it potentially useful as a safe form of a live vaccine against HSV. We previously demonstrated that mice generate a stronger response to ICP8- virus encoding B7-2 costimulation molecules than to the parental replication-defective virus. We have also demonstrated enhanced immunogenicity of an ICP8-, virion host shutoff (vhs)- virus which can no longer destabilize viral and host mRNAs. Here, we constructed a triple mutant, ICP8-vhs-B7-2+ strain, and compared it to both double mutant viruses. Immunization of mice with a single dose of ICP8-B7-2+ or ICP8-vhs-B7-2+ virus decreased challenge virus replication in the vaginal mucosa, genital disease, and mortality more effectively than immunization with the ICP8-vhs- virus. Immunization with ICP8-B7-2+ or ICP8-vhs-B7-2+ virus also effectively suppressed subsequent HSV-2 infection of the nervous system compared to immunization with the ICP8-vhs- virus. ICP8-B7-2+ and ICP8-vhs-B7-2+ strains induced more IFN gamma-producing CD8 T cells and memory CD8 T cells than did ICP8-vhs- virus, potentially explaining the enhanced protective effects. Thus, B7 costimulation molecules expressed from a replication-defective vaccine can enhance vaccine efficacy, even in an immunocompetent host. Full article

(This article belongs to the Special Issue Efficacy, Safety, and Immunogenicity of Vaccines against Viruses: From Network Medicine to Clinical Experimentation)

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19 pages, 3747 KiB

Open AccessArticle

Prediction of Antigenic Distance in Influenza A Using Attribute Network Embedding

by Fujun Peng, Yuanling Xia and Weihua Li

Viruses 2023, 15(7), 1478; https://doi.org/10.3390/v15071478 - 29 Jun 2023

Viewed by 1553

Abstract

Owing to the rapid changes in the antigenicity of influenza viruses, it is difficult for humans to obtain lasting immunity through antiviral therapy. Hence, tracking the dynamic changes in the antigenicity of influenza viruses can provide a basis for vaccines and drug treatments [...] Read more.

Owing to the rapid changes in the antigenicity of influenza viruses, it is difficult for humans to obtain lasting immunity through antiviral therapy. Hence, tracking the dynamic changes in the antigenicity of influenza viruses can provide a basis for vaccines and drug treatments to cope with the spread of influenza viruses. In this paper, we developed a novel quantitative prediction method to predict the antigenic distance between virus strains using attribute network embedding techniques. An antigenic network is built to model and combine the genetic and antigenic characteristics of the influenza A virus H3N2, using the continuous distributed representation of the virus strain protein sequence (ProtVec) as a node attribute and the antigenic distance between virus strains as an edge weight. The results show a strong positive correlation between supplementing genetic features and antigenic distance prediction accuracy. Further analysis indicates that our prediction model can comprehensively and accurately track the differences in antigenic distances between vaccines and influenza virus strains, and it outperforms existing methods in predicting antigenic distances between strains. Full article

(This article belongs to the Special Issue Efficacy, Safety, and Immunogenicity of Vaccines against Viruses: From Network Medicine to Clinical Experimentation)

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20 pages, 5143 KiB

Open AccessArticle

Development of a Multi-Epitope Universal mRNA Vaccine Candidate for Monkeypox, Smallpox, and Vaccinia Viruses: Design and In Silico Analyses

by Nino Rcheulishvili, Jiawei Mao, Dimitri Papukashvili, Shunping Feng, Cong Liu, Xidan Yang, Jihui Lin, Yunjiao He and Peng George Wang

Viruses 2023, 15(5), 1120; https://doi.org/10.3390/v15051120 - 07 May 2023

Cited by 6 | Viewed by 2690

Abstract

Notwithstanding the presence of a smallpox vaccine that is effective against monkeypox (mpox), developing a universal vaccine candidate against monkeypox virus (MPXV) is highly required as the mpox multi-country outbreak has increased global concern. MPXV, along with variola virus (VARV) and vaccinia virus [...] Read more.

Notwithstanding the presence of a smallpox vaccine that is effective against monkeypox (mpox), developing a universal vaccine candidate against monkeypox virus (MPXV) is highly required as the mpox multi-country outbreak has increased global concern. MPXV, along with variola virus (VARV) and vaccinia virus (VACV), belongs to the Orthopoxvirus genus. Due to the genetic similarity of antigens in this study, we have designed a potentially universal mRNA vaccine based on conserved epitopes that are specific to these three viruses. In order to design a potentially universal mRNA vaccine, antigens A29, A30, A35, B6, and M1 were selected. The conserved sequences among the three viral species—MPXV, VACV, and VARV—were detected, and B and T cell epitopes containing the conserved elements were used for the design of the multi-epitope mRNA construct. Immunoinformatics analyses demonstrated the stability of the vaccine construct and optimal binding to MHC molecules. Humoral and cellular immune responses were induced by immune simulation analyses. Eventually, based on in silico analysis, the universal mRNA multi-epitope vaccine candidate designed in this study may have a potential protection against MPXV, VARV, and VACV that will contribute to the advancement of prevention strategies for unpredictable pandemics. Full article

(This article belongs to the Special Issue Efficacy, Safety, and Immunogenicity of Vaccines against Viruses: From Network Medicine to Clinical Experimentation)

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Review

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23 pages, 794 KiB

Open AccessReview

Immunogenicity and Efficacy of Vaccination in People Living with Human Immunodeficiency Virus

by Eeva Tortellini, Yann Collins Fosso Ngangue, Federica Dominelli, Mariasilvia Guardiani, Carmen Falvino, Fabio Mengoni, Anna Carraro, Raffaella Marocco, Patrizia Pasculli, Claudio Maria Mastroianni, Maria Rosa Ciardi, Miriam Lichtner and Maria Antonella Zingaropoli

Viruses 2023, 15(9), 1844; https://doi.org/10.3390/v15091844 - 30 Aug 2023

Cited by 1 | Viewed by 1696

Abstract

People living with HIV (PLWH) remain at high risk of mortality and morbidity from vaccine-preventable diseases, even though antiretroviral therapy (ART) has restored life expectancy and general well-being. When, which, and how many doses of vaccine should be administered over the lifetime of [...] Read more.

People living with HIV (PLWH) remain at high risk of mortality and morbidity from vaccine-preventable diseases, even though antiretroviral therapy (ART) has restored life expectancy and general well-being. When, which, and how many doses of vaccine should be administered over the lifetime of PLWH are questions that have become clinically relevant. Immune responses to most vaccines are known to be impaired in PLWH. Effective control of viremia with ART and restored CD4+ T-cell count are correlated with an improvement in responsiveness to routine vaccines. However, the presence of immune alterations, comorbidities and co-infections may alter it. In this article, we provide a comprehensive review of the literature on immune responses to different vaccines in the setting of HIV infection, emphasizing the potential effect of HIV-related factors and presence of comorbidities in modulating such responses. A better understanding of these issues will help guide vaccination and prevention strategies for PLWH. Full article

(This article belongs to the Special Issue Efficacy, Safety, and Immunogenicity of Vaccines against Viruses: From Network Medicine to Clinical Experimentation)

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