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13 pages, 1922 KiB

Open AccessArticle

NIgPred: Class-Specific Antibody Prediction for Linear B-Cell Epitopes Based on Heterogeneous Features and Machine-Learning Approaches

by Chi-Hua Tung, Yi-Sheng Chang, Kai-Po Chang and Yen-Wei Chu

Viruses 2021, 13(8), 1531; https://0-doi-org.brum.beds.ac.uk/10.3390/v13081531 - 03 Aug 2021

Cited by 4 | Viewed by 2487

Abstract

Upon invasion by foreign pathogens, specific antibodies can identify specific foreign antigens and disable them. As a result of this ability, antibodies can help with vaccine production and food allergen detection in patients. Many studies have focused on predicting linear B-cell epitopes, but [...] Read more.

Upon invasion by foreign pathogens, specific antibodies can identify specific foreign antigens and disable them. As a result of this ability, antibodies can help with vaccine production and food allergen detection in patients. Many studies have focused on predicting linear B-cell epitopes, but only two prediction tools are currently available to predict the sub-type of an epitope. NIgPred was developed as a prediction tool for IgA, IgE, and IgG. NIgPred integrates various heterologous features with machine-learning approaches. Differently from previous studies, our study considered peptide-characteristic correlation and autocorrelation features. Sixty kinds of classifier were applied to construct the best prediction model. Furthermore, the genetic algorithm and hill-climbing algorithm were used to select the most suitable features for improving the accuracy and reducing the time complexity of the training model. NIgPred was found to be superior to the currently available tools for predicting IgE epitopes and IgG epitopes on independent test sets. Moreover, NIgPred achieved a prediction accuracy of 100% for the IgG epitopes of a coronavirus data set. NIgPred is publicly available at our website. Full article

(This article belongs to the Special Issue Influenza Virus Vaccines)

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10 pages, 1253 KiB

Open AccessArticle

Autoreactivity of Broadly Neutralizing Influenza Human Antibodies to Human Tissues and Human Proteins

by Surender Khurana, Megan Hahn, Laura Klenow and Hana Golding

Viruses 2020, 12(10), 1140; https://0-doi-org.brum.beds.ac.uk/10.3390/v12101140 - 08 Oct 2020

Cited by 11 | Viewed by 2634

Abstract

Broadly neutralizing monoclonal antibodies (bNAbs) against conserved domains in the influenza hemagglutinin are in clinical trials. Several next generation influenza vaccines designed to elicit such bNAbs are also in clinical development. One of the common features of the isolated bNAbs is the use [...] Read more.

Broadly neutralizing monoclonal antibodies (bNAbs) against conserved domains in the influenza hemagglutinin are in clinical trials. Several next generation influenza vaccines designed to elicit such bNAbs are also in clinical development. One of the common features of the isolated bNAbs is the use of restricted IgV_H repertoire. More than 80% of stem-targeting bNAbs express IgV_H1-69, which may indicate genetic constraints on the evolution of such antibodies. In the current study, we evaluated a panel of influenza virus bNAbs in comparison with HIV-1 MAb 4E10 and anti-RSV MAb Palivizumab (approved for human use) for autoreactivity using 30 normal human tissues microarray and human protein (>9000) arrays. We found that several human bNAbs (CR6261, CR9114, and F2603) reacted with human tissues, especially with pituitary gland tissue. Importantly, protein array analysis identified high-affinity interaction of CR6261 with the autoantigen “Enhancer of mRNA decapping 3 homolog” (EDC3), which was not previously described. Moreover, EDC3 competed with hemagglutinin for binding to bNAb CR6261. These autoreactivity findings underscores the need for careful evaluation of such bNAbs for therapeutics and stem-based vaccines against influenza virus. Full article

(This article belongs to the Special Issue Influenza Virus Vaccines)

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11 pages, 2286 KiB

Open AccessArticle

Highly Immunogenic Nanoparticles Based on a Fusion Protein Comprising the M2e of Influenza A Virus and a Lipopeptide

by Anna A. Zykova, Elena A. Blokhina, Roman Y. Kotlyarov, Liudmila A. Stepanova, Liudmila M. Tsybalova, Victor V. Kuprianov and Nikolai V. Ravin

Viruses 2020, 12(10), 1133; https://0-doi-org.brum.beds.ac.uk/10.3390/v12101133 - 06 Oct 2020

Cited by 5 | Viewed by 2301

Abstract

The highly conserved extracellular domain of the transmembrane protein M2 (M2e) of the influenza A virus is a promising target for the development of broad-spectrum vaccines. However, M2e is a poor immunogen by itself and must be linked to an appropriate carrier to [...] Read more.

The highly conserved extracellular domain of the transmembrane protein M2 (M2e) of the influenza A virus is a promising target for the development of broad-spectrum vaccines. However, M2e is a poor immunogen by itself and must be linked to an appropriate carrier to induce an efficient immune response. In this study, we obtained recombinant mosaic proteins containing tandem copies of M2e fused to a lipopeptide from Neisseria meningitidis surface lipoprotein Ag473 and alpha-helical linkers and analyzed their immunogenicity. Six fusion proteins, comprising four or eight tandem copies of M2e flanked by alpha-helical linkers, lipopeptides, or a combination of both of these elements, were produced in Escherichia coli. The proteins, containing both alpha-helical linkers and lipopeptides at each side of M2e repeats, formed nanosized particles, but no particulate structures were observed in the absence of lipopeptides. Animal study results showed that proteins with lipopeptides induced strong M2e-specific antibody responses in the absence of external adjuvants compared to similar proteins without lipopeptides. Thus, the recombinant M2e-based proteins containing alpha-helical linkers and N. meningitidis lipopeptide sequences at the N- and C-termini of four or eight tandem copies of M2e peptide are promising vaccine candidates. Full article

(This article belongs to the Special Issue Influenza Virus Vaccines)

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21 pages, 1997 KiB

Open AccessArticle

Efficacy of Heterologous Prime-Boost Vaccination with H3N2 Influenza Viruses in Pre-Immune Individuals: Studies in the Pig Model

by Sharon Chepkwony, Anna Parys, Elien Vandoorn, Koen Chiers and Kristien Van Reeth

Viruses 2020, 12(9), 968; https://0-doi-org.brum.beds.ac.uk/10.3390/v12090968 - 01 Sep 2020

Cited by 10 | Viewed by 2499

Abstract

In a previous study in influenza-naïve pigs, heterologous prime-boost vaccination with monovalent, adjuvanted whole inactivated vaccines (WIV) based on the European swine influenza A virus (SwIAV) strain, A/swine/Gent/172/2008 (G08), followed by the US SwIAV strain, A/swine/Pennsylvania/A01076777/2010 (PA10), was shown to induce broadly cross-reactive [...] Read more.

In a previous study in influenza-naïve pigs, heterologous prime-boost vaccination with monovalent, adjuvanted whole inactivated vaccines (WIV) based on the European swine influenza A virus (SwIAV) strain, A/swine/Gent/172/2008 (G08), followed by the US SwIAV strain, A/swine/Pennsylvania/A01076777/2010 (PA10), was shown to induce broadly cross-reactive hemagglutination inhibition (HI) antibodies against 12 out of 15 antigenically distinct H3N2 influenza strains. Here, we used the pig model to examine the efficacy of that particular heterologous prime-boost vaccination regimen, in individuals with pre-existing infection-immunity. Pigs were first inoculated intranasally with the human H3N2 strain, A/Nanchang/933/1995. Seven weeks later, they were vaccinated intramuscularly with G08 followed by PA10 or vice versa. We examined serum antibody responses against the hemagglutinin and neuraminidase, and antibody-secreting cell (ASC) responses in peripheral blood, draining lymph nodes, and nasal mucosa (NMC), in ELISPOT assays. Vaccination induced up to 10-fold higher HI antibody titers than in naïve pigs, with broader cross-reactivity, and protection against challenge with an antigenically distant H3N2 strain. It also boosted ASC responses in lymph nodes and NMC. Our results show that intramuscular administration of WIV can lead to enhanced antibody responses and cross-reactivity in pre-immune subjects, and recall of ASC responses in lymph nodes and NMC. Full article

(This article belongs to the Special Issue Influenza Virus Vaccines)

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15 pages, 3536 KiB

Open AccessArticle

Comparative Analyses of the Antiviral Activities of IgG and IgA Antibodies to Influenza A Virus M2 Protein

by Kosuke Okuya, Nao Eguchi, Rashid Manzoor, Reiko Yoshida, Shinji Saito, Tadaki Suzuki, Michihito Sasaki, Takeshi Saito, Yurie Kida, Akina Mori-Kajihara, Hiroko Miyamoto, Osamu Ichii, Masahiro Kajihara, Hideaki Higashi and Ayato Takada

Viruses 2020, 12(7), 780; https://0-doi-org.brum.beds.ac.uk/10.3390/v12070780 - 20 Jul 2020

Cited by 4 | Viewed by 3219

Abstract

The influenza A virus (IAV) matrix-2 (M2) protein is an antigenically conserved viral envelope protein that plays an important role in virus budding together with another envelope protein, hemagglutinin (HA). An M2-specific mouse monoclonal IgG antibody, rM2ss23, which binds to the ectodomain of [...] Read more.

The influenza A virus (IAV) matrix-2 (M2) protein is an antigenically conserved viral envelope protein that plays an important role in virus budding together with another envelope protein, hemagglutinin (HA). An M2-specific mouse monoclonal IgG antibody, rM2ss23, which binds to the ectodomain of the M2 protein, has been shown to be a non-neutralizing antibody, but inhibits plaque formation of IAV strains. In this study, we generated chimeric rM2ss23 (ch-rM2ss23) IgG and IgA antibodies with the same variable region and compared their antiviral activities. Using gel chromatography, ch-rM2ss23 IgA were divided into three antibody subsets: monomeric IgA (m-IgA), dimeric IgA (d-IgA), and trimeric and tetrameric IgA (t/q-IgA). We found that t/q-IgA had a significantly higher capacity to reduce the plaque size of IAVs than IgG and m-IgA, most likely due to the decreased number of progeny virus particles produced from infected cells. Interestingly, HA-M2 colocalization was remarkably reduced on the infected cell surface in the presence of ch-rM2ss23 antibodies. These results indicate that anti-M2 polymeric IgA restricts IAV budding more efficiently than IgG and suggest a role of anti-M2 IgA in cross-protective immunity to IAVs. Full article

(This article belongs to the Special Issue Influenza Virus Vaccines)

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Review

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10 pages, 983 KiB

Open AccessReview

Influenza Vaccines toward Universality through Nanoplatforms and Given by Microneedle Patches

by Sijia Tang, Wandi Zhu and Bao-Zhong Wang

Viruses 2020, 12(11), 1212; https://0-doi-org.brum.beds.ac.uk/10.3390/v12111212 - 24 Oct 2020

Cited by 4 | Viewed by 3423

Abstract

Influenza is one of the top threats to public health. The best strategy to prevent influenza is vaccination. Because of the antigenic changes in the major surface antigens of influenza viruses, current seasonal influenza vaccines need to be updated every year to match [...] Read more.

Influenza is one of the top threats to public health. The best strategy to prevent influenza is vaccination. Because of the antigenic changes in the major surface antigens of influenza viruses, current seasonal influenza vaccines need to be updated every year to match the circulating strains and are suboptimal for protection. Furthermore, seasonal vaccines do not protect against potential influenza pandemics. A universal influenza vaccine will eliminate the threat of both influenza epidemics and pandemics. Due to the massive challenge in realizing influenza vaccine universality, a single vaccine strategy cannot meet the need. A comprehensive approach that integrates advances in immunogen designs, vaccine and adjuvant nanoplatforms, and vaccine delivery and controlled release has the potential to achieve an effective universal influenza vaccine. This review will summarize the advances in the research and development of an affordable universal influenza vaccine. Full article

(This article belongs to the Special Issue Influenza Virus Vaccines)

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22 pages, 2371 KiB

Open AccessReview

A Decade in Review: A Systematic Review of Universal Influenza Vaccines in Clinical Trials during the 2010 Decade

by Brigette N. Corder, Brianna L. Bullard, Gregory A. Poland and Eric A. Weaver

Viruses 2020, 12(10), 1186; https://0-doi-org.brum.beds.ac.uk/10.3390/v12101186 - 20 Oct 2020

Cited by 23 | Viewed by 4585

Abstract

On average, there are 3–5 million severe cases of influenza virus infections globally each year. Seasonal influenza vaccines provide limited protection against divergent influenza strains. Therefore, the development of a universal influenza vaccine is a top priority for the NIH. Here, we report [...] Read more.

On average, there are 3–5 million severe cases of influenza virus infections globally each year. Seasonal influenza vaccines provide limited protection against divergent influenza strains. Therefore, the development of a universal influenza vaccine is a top priority for the NIH. Here, we report a comprehensive summary of all universal influenza vaccines that were tested in clinical trials during the 2010–2019 decade. Of the 1597 studies found, 69 eligible clinical trials, which investigated 27 vaccines, were included in this review. Information from each trial was compiled for vaccine target, vaccine platform, adjuvant inclusion, clinical trial phase, and results. As we look forward, there are currently three vaccines in phase III clinical trials which could provide significant improvement over seasonal influenza vaccines. This systematic review of universal influenza vaccine clinical trials during the 2010–2019 decade provides an update on the progress towards an improved influenza vaccine. Full article

(This article belongs to the Special Issue Influenza Virus Vaccines)

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19 pages, 5398 KiB

Open AccessReview

Progress in the Development of Universal Influenza Vaccines

by Wenqiang Sun, Tingrong Luo, Wenjun Liu and Jing Li

Viruses 2020, 12(9), 1033; https://doi.org/10.3390/v12091033 - 17 Sep 2020

Cited by 28 | Viewed by 4819

Abstract

Influenza viruses pose a significant threat to human health. They are responsible for a large number of deaths annually and have a serious impact on the global economy. There are numerous influenza virus subtypes, antigenic variations occur continuously, and epidemic trends are difficult [...] Read more.

Influenza viruses pose a significant threat to human health. They are responsible for a large number of deaths annually and have a serious impact on the global economy. There are numerous influenza virus subtypes, antigenic variations occur continuously, and epidemic trends are difficult to predict—all of which lead to poor outcomes of routine vaccination against targeted strain subtypes. Therefore, the development of universal influenza vaccines still constitutes the ideal strategy for controlling influenza. This article reviews the progress in development of universal vaccines directed against the conserved regions of hemagglutinin (HA), neuraminidase (NA), and other structural proteins of influenza viruses using new technologies and strategies with the goals of enhancing our understanding of universal influenza vaccines and providing a reference for research into the exploitation of natural immunity against influenza viruses. Full article

(This article belongs to the Special Issue Influenza Virus Vaccines)

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20 pages, 1515 KiB

Open AccessReview

Influenza A Virus Antibodies with Antibody-Dependent Cellular Cytotoxicity Function

by Rongyuan Gao, Zizhang Sheng, Chithra C. Sreenivasan, Dan Wang and Feng Li

Viruses 2020, 12(3), 276; https://0-doi-org.brum.beds.ac.uk/10.3390/v12030276 - 01 Mar 2020

Cited by 22 | Viewed by 5396

Abstract

Influenza causes millions of cases of hospitalizations annually and remains a public health concern on a global scale. Vaccines are developed and have proven to be the most effective countermeasures against influenza infection. Their efficacy has been largely evaluated by hemagglutinin inhibition (HI) [...] Read more.

Influenza causes millions of cases of hospitalizations annually and remains a public health concern on a global scale. Vaccines are developed and have proven to be the most effective countermeasures against influenza infection. Their efficacy has been largely evaluated by hemagglutinin inhibition (HI) titers exhibited by vaccine-induced neutralizing antibodies, which correlate fairly well with vaccine-conferred protection. Contrarily, non-neutralizing antibodies and their therapeutic potential are less well defined, yet, recent advances in anti-influenza antibody research indicate that non-neutralizing Fc-effector activities, especially antibody-dependent cellular cytotoxicity (ADCC), also serve as a critical mechanism in antibody-mediated anti-influenza host response. Monoclonal antibodies (mAbs) with Fc-effector activities have the potential for prophylactic and therapeutic treatment of influenza infection. Inducing mAbs mediated Fc-effector functions could be a complementary or alternative approach to the existing neutralizing antibody-based prevention and therapy. This review mainly discusses recent advances in Fc-effector functions, especially ADCC and their potential role in influenza countermeasures. Considering the complexity of anti-influenza approaches, future vaccines may need a cocktail of immunogens in order to elicit antibodies with broad-spectrum protection via multiple protective mechanisms. Full article

(This article belongs to the Special Issue Influenza Virus Vaccines)

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