Pathogens

Editorial

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2 pages, 170 KiB

Open AccessEditorial

Influenza Virus and Vaccination

by Aitor Nogales and Marta L. DeDiego

Pathogens 2020, 9(3), 220; https://doi.org/10.3390/pathogens9030220 - 17 Mar 2020

Cited by 5 | Viewed by 2549

Abstract

Influenza virus infections represent a serious public health problem causing contagious respiratory disease and substantial morbidity and mortality in humans, resulting in a considerable economic burden worldwide. Notably, the number of deaths due to influenza exceeds that of any other known pathogen. Moreover, [...] Read more.

Influenza virus infections represent a serious public health problem causing contagious respiratory disease and substantial morbidity and mortality in humans, resulting in a considerable economic burden worldwide. Notably, the number of deaths due to influenza exceeds that of any other known pathogen. Moreover, influenza infections can differ in their intensity, from mild respiratory disease to pneumonia, which can lead to death. Articles in this Special Issue have addressed different aspects of influenza in human health, and the advances in influenza research leading to the development of better therapeutics and vaccination strategies, with a special focus on the study of factors associated with innate or adaptive immune responses to influenza vaccination and/or infection. Full article

(This article belongs to the Special Issue Influenza Virus and Vaccination)

Research

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18 pages, 2264 KiB

Open AccessEditor’s ChoiceArticle

Increasing the Safety Profile of the Master Donor Live Attenuated Influenza Vaccine

by Thomas A. Hilimire, Aitor Nogales, Kevin Chiem, Javier Ortego and Luis Martinez-Sobrido

Pathogens 2020, 9(2), 86; https://doi.org/10.3390/pathogens9020086 - 29 Jan 2020

Cited by 15 | Viewed by 2427

Abstract

Seasonal influenza epidemics remain one of the largest public health burdens nowadays. The best and most effective strategy to date in preventing influenza infection is a worldwide vaccination campaign. Currently, two vaccines are available to the public for the treatment of influenza infection, [...] Read more.

Seasonal influenza epidemics remain one of the largest public health burdens nowadays. The best and most effective strategy to date in preventing influenza infection is a worldwide vaccination campaign. Currently, two vaccines are available to the public for the treatment of influenza infection, the chemically Inactivated Influenza Vaccine (IIV) and the Live Attenuated Influenza Vaccine (LAIV). However, the LAIV is not recommended for parts of the population, such as children under the age of two, immunocompromised individuals, the elderly, and pregnant adults. In order to improve the safety of the LAIV and make it available to more of the population, we sought to further attenuate the LAIV. In this study, we demonstrate that the influenza A virus (IAV) master donor virus (MDV) A/Ann Arbor/6/60 H2N2 LAIV can inhibit host gene expression using both the PA-X and NS1 proteins. Furthermore, we show that by removing PA-X, we can limit the replication of the MDV LAIV in a mouse model, while maintaining full protective efficacy. This work demonstrates a broadly applicable strategy of tuning the amount of host antiviral responses induced by the IAV MDV for the development of newer and safer LAIVs. Moreover, our results also demonstrate, for the first time, the feasibility of genetically manipulating the backbone of the IAV MDV to improve the efficacy of the current IAV LAIV. Full article

(This article belongs to the Special Issue Influenza Virus and Vaccination)

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15 pages, 2519 KiB

Open AccessArticle

Peptide Epitope Hot Spots of CD4 T Cell Recognition Within Influenza Hemagglutinin During the Primary Response to Infection

by Zackery A. G. Knowlden, Katherine A. Richards, Savannah A. Moritzky and Andrea J. Sant

Pathogens 2019, 8(4), 220; https://doi.org/10.3390/pathogens8040220 - 05 Nov 2019

Cited by 10 | Viewed by 3822

Abstract

Antibodies specific for the hemagglutinin (HA) protein of influenza virus are critical for protective immunity to infection. Our studies show that CD4 T cells specific for epitopes derived from HA are the most effective in providing help for the HA-specific B cell responses [...] Read more.

Antibodies specific for the hemagglutinin (HA) protein of influenza virus are critical for protective immunity to infection. Our studies show that CD4 T cells specific for epitopes derived from HA are the most effective in providing help for the HA-specific B cell responses to infection and vaccination. In this study, we asked whether HA epitopes recognized by CD4 T cells in the primary response to infection are equally distributed across the HA protein or if certain segments are enriched in CD4 T cell epitopes. Mice that collectively expressed eight alternative MHC (Major Histocompatibility Complex) class II molecules, that would each have different peptide binding specificities, were infected with an H1N1 influenza virus. CD4 T cell peptide epitope specificities were identified by cytokine EliSpots. These studies revealed that the HA-specific CD4 T cell epitopes cluster in two distinct regions of HA and that some segments of HA are completely devoid of CD4 T cell epitopes. When located on the HA structure, it appears that the regions that most poorly recruit CD4 T cells are sequestered within the interior of the HA trimer, perhaps inaccessible to the proteolytic machinery inside the endosomal compartments of antigen presenting cells. Full article

(This article belongs to the Special Issue Influenza Virus and Vaccination)

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Review

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24 pages, 1341 KiB

Open AccessReview

The Importance of Vaccinating Children and Pregnant Women against Influenza Virus Infection

by Ravi S Misra and Jennifer L Nayak

Pathogens 2019, 8(4), 265; https://doi.org/10.3390/pathogens8040265 - 26 Nov 2019

Cited by 7 | Viewed by 5391

Abstract

Influenza virus infection is responsible for significant morbidity and mortality in the pediatric and pregnant women populations, with deaths frequently caused by severe influenza-associated lower respiratory tract infection and acute respiratory distress syndrome (ARDS). An appropriate immune response requires controlling the viral infection [...] Read more.

Influenza virus infection is responsible for significant morbidity and mortality in the pediatric and pregnant women populations, with deaths frequently caused by severe influenza-associated lower respiratory tract infection and acute respiratory distress syndrome (ARDS). An appropriate immune response requires controlling the viral infection through activation of antiviral defenses, which involves cells of the lung and immune system. High levels of viral infection or high levels of inflammation in the lower airways can contribute to ARDS. Pregnant women and young children, especially those born prematurely, may develop serious complications if infected with influenza virus. Vaccination against influenza virus will lead to lower infection rates and fewer complications, even if the vaccine is poorly matched to circulating viral strains. Maternal vaccination offers infants protection via antibody transmission through the placenta and breast milk. Despite the health benefits of the influenza vaccine, vaccination rates around the world remain well below targets. Trust in the use of vaccines among the public must be restored in order to increase vaccination rates and decrease the public health burden of influenza. Full article

(This article belongs to the Special Issue Influenza Virus and Vaccination)

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17 pages, 5895 KiB

Open AccessReview

A Complex Dance: Measuring the Multidimensional Worlds of Influenza Virus Evolution and Anti-Influenza Immune Responses

by Jiong Wang, Alexander Wiltse and Martin S. Zand

Pathogens 2019, 8(4), 238; https://doi.org/10.3390/pathogens8040238 - 15 Nov 2019

Cited by 8 | Viewed by 3722

Abstract

The human antibody response to influenza virus infection or vaccination is as complicated as it is essential for protection against flu. The constant antigenic changes of the virus to escape human herd immunity hinder the yearly selection of vaccine strains since it is [...] Read more.

The human antibody response to influenza virus infection or vaccination is as complicated as it is essential for protection against flu. The constant antigenic changes of the virus to escape human herd immunity hinder the yearly selection of vaccine strains since it is hard to predict which virus strains will circulate for the coming flu season. A “universal” influenza vaccine that could induce broad cross-influenza subtype protection would help to address this issue. However, the human antibody response is intricate and often obscure, with factors such as antigenic seniority or original antigenic sin (OAS), and back-boosting ensuring that each person mounts a unique immune response to infection or vaccination with any new influenza virus strain. Notably, the effects of existing antibodies on cross-protective immunity after repeated vaccinations are unclear. More research is needed to characterize the mechanisms at play, but traditional assays such as hemagglutinin inhibition (HAI) and microneutralization (MN) are excessively limited in scope and too resource-intensive to effectively meet this challenge. In the past ten years, new multiple dimensional assays (MDAs) have been developed to help overcome these problems by simultaneously measuring antibodies against a large panel of influenza hemagglutinin (HA) proteins with a minimal amount of sample in a high throughput way. MDAs will likely be a powerful tool for accelerating the study of the humoral immune response to influenza vaccination and the development of a universal influenza vaccine. Full article

(This article belongs to the Special Issue Influenza Virus and Vaccination)

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9 pages, 2769 KiB

Open AccessEditor’s ChoiceReview

Formation and Maintenance of Tissue Resident Memory CD8+ T Cells after Viral Infection

by David J. Topham, Emma C. Reilly, Kris Lambert Emo and Mike Sportiello

Pathogens 2019, 8(4), 196; https://doi.org/10.3390/pathogens8040196 - 18 Oct 2019

Cited by 6 | Viewed by 3893

Abstract

Tissue resident memory (T_RM) CD8 T cells comprise a memory population that forms in peripheral, non-lymphoid tissues after an infection that does not recirculate into the bloodstream or other tissues. T_RM cells often recognize conserved peptide epitopes shared among different [...] Read more.

Tissue resident memory (T_RM) CD8 T cells comprise a memory population that forms in peripheral, non-lymphoid tissues after an infection that does not recirculate into the bloodstream or other tissues. T_RM cells often recognize conserved peptide epitopes shared among different strains of a pathogen and so offer a protective role upon secondary encounter with the same or related pathogens. Several recent studies have begun to shed light on the intrinsic and extrinsic factors regulating T_RM. In addition, work is being done to understand how canonical “markers” of T_RM actually affect the function of these cells. Many of these markers regulate the generation or persistence of these T_RM cells, an important point of study due to the differences in persistence of T_RM between tissues, which may impact future vaccine development to cater towards these important differences. In this review, we will discuss recent advances in T_RM biology that may lead to strategies designed to promote this important protective immune subset. Full article

(This article belongs to the Special Issue Influenza Virus and Vaccination)

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22 pages, 906 KiB

Open AccessEditor’s ChoiceReview

Host Single Nucleotide Polymorphisms Modulating Influenza A Virus Disease in Humans

by Aitor Nogales and Marta L. DeDiego

Pathogens 2019, 8(4), 168; https://doi.org/10.3390/pathogens8040168 - 30 Sep 2019

Cited by 26 | Viewed by 7265

Abstract

A large number of human genes associated with viral infections contain single nucleotide polymorphisms (SNPs), which represent a genetic variation caused by the change of a single nucleotide in the DNA sequence. SNPs are located in coding or non-coding genomic regions and can [...] Read more.

A large number of human genes associated with viral infections contain single nucleotide polymorphisms (SNPs), which represent a genetic variation caused by the change of a single nucleotide in the DNA sequence. SNPs are located in coding or non-coding genomic regions and can affect gene expression or protein function by different mechanisms. Furthermore, they have been linked to multiple human diseases, highlighting their medical relevance. Therefore, the identification and analysis of this kind of polymorphisms in the human genome has gained high importance in the research community, and an increasing number of studies have been published during the last years. As a consequence of this exhaustive exploration, an association between the presence of some specific SNPs and the susceptibility or severity of many infectious diseases in some risk population groups has been found. In this review, we discuss the relevance of SNPs that are important to understand the pathology derived from influenza A virus (IAV) infections in humans and the susceptibility of some individuals to suffer more severe symptoms. We also discuss the importance of SNPs for IAV vaccine effectiveness. Full article

(This article belongs to the Special Issue Influenza Virus and Vaccination)

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13 pages, 1114 KiB

Open AccessEditor’s ChoiceReview

Role of Memory B Cells in Hemagglutinin-Specific Antibody Production Following Human Influenza A Virus Infection

by Mark Y. Sangster, Phuong Q. T. Nguyen and David J. Topham

Pathogens 2019, 8(4), 167; https://doi.org/10.3390/pathogens8040167 - 28 Sep 2019

Cited by 18 | Viewed by 6276

Abstract

When influenza A virus infects an immune individual, preexisting memory B cell (MBC) activation and rapid anamnestic antibody production plays a key role in viral clearance. The most effective neutralizing antibodies target the antigenically variable head of the viral hemagglutinin (HA); antibodies against [...] Read more.

When influenza A virus infects an immune individual, preexisting memory B cell (MBC) activation and rapid anamnestic antibody production plays a key role in viral clearance. The most effective neutralizing antibodies target the antigenically variable head of the viral hemagglutinin (HA); antibodies against the conserved HA stalk provide broader but less potent protection. In this review, we provide a comprehensive picture of an adult’s HA-specific antibody response to influenza virus infection. The process is followed from preexisting HA-specific MBC activation and rapid production of anti-HA antibodies, through to germinal center seeding and adaptation of the response to novel features of the HA. A major focus of the review is the role of competition between preexisting MBCs in determining the character of the HA-reactive antibody response. HA novelty modifies this competition and can shift the response from the immunodominant head to the stalk. We suggest that antibodies resulting from preexisting MBC activation are important regulators of anti-HA antibody production and play a role in positive selection of germinal center B cells reactive to novel HA epitopes. Our review also considers the role of MBCs in the effects of early-life imprinting on HA head- and stalk-specific antibody responses to influenza infection. An understanding of the processes described in this review will guide development of vaccination strategies that provide broadly effective protection. Full article

(This article belongs to the Special Issue Influenza Virus and Vaccination)

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