scholarly journals B Cell Responses against Influenza Viruses: Short-Lived Humoral Immunity against a Life-Long Threat

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 965
Author(s):  
Jenna J. Guthmiller ◽  
Henry A. Utset ◽  
Patrick C. Wilson
Keyword(s):  
B Cells ◽  
Humoral Immunity ◽  
Influenza A ◽  
Neutralizing Antibody ◽  
Memory B Cells ◽  
Influenza Viruses ◽  
Antigenic Drift ◽  
Virus Infections ◽  
Influenza A Viruses ◽  
Major Surface

Antibodies are critical for providing protection against influenza virus infections. However, protective humoral immunity against influenza viruses is limited by the antigenic drift and shift of the major surface glycoproteins, hemagglutinin and neuraminidase. Importantly, people are exposed to influenza viruses throughout their life and tend to reuse memory B cells from prior exposure to generate antibodies against new variants. Despite this, people tend to recall memory B cells against constantly evolving variable epitopes or non-protective antigens, as opposed to recalling them against broadly neutralizing epitopes of hemagglutinin. In this review, we discuss the factors that impact the generation and recall of memory B cells against distinct viral antigens, as well as the immunological limitations preventing broadly neutralizing antibody responses. Lastly, we discuss how next-generation vaccine platforms can potentially overcome these obstacles to generate robust and long-lived protection against influenza A viruses.

scholarly journals Induction of Virus-Specific Cytotoxic T Lymphocytes as a Basis for the Development of Broadly Protective Influenza Vaccines

2011 ◽  
Vol 2011 ◽  
pp. 1-12 ◽  
Author(s):  
Marine L. B. Hillaire ◽  
Albert D. M. E. Osterhaus ◽  
Guus F. Rimmelzwaan
Keyword(s):  
T Lymphocytes ◽  
Influenza A Virus ◽  
Cytotoxic T Lymphocytes ◽  
Influenza A ◽  
Influenza Viruses ◽  
Antigenic Drift ◽  
Influenza Vaccines ◽  
Virus Infections ◽  
Influenza A Viruses ◽  
Heterosubtypic Immunity

There is considerable interest in the development of broadly protective influenza vaccines because of the continuous emergence of antigenic drift variants of seasonal influenza viruses and the threat posed by the emergence of antigenically distinct pandemic influenza viruses. It has been recognized more than three decades ago that influenza A virus-specific cytotoxic T lymphocytes recognize epitopes located in the relatively conserved proteins like the nucleoprotein and that they cross-react with various subtypes of influenza A viruses. This implies that these CD8+T lymphocytes may contribute to protective heterosubtypic immunity induced by antecedent influenza A virus infections. In the present paper, we review the evidence for the role of virus-specific CD8+T lymphocytes in protective immunity against influenza virus infections and discuss vaccination strategies that aim at the induction of cross-reactive virus-specific T-cell responses.

scholarly journals Memory B Cells that Cross-React with Group 1 and Group 2 Influenza A Viruses Are Abundant in Adult Human Repertoires

Immunity ◽  
2018 ◽  
Vol 48 (1) ◽  
pp. 174-184.e9 ◽  
Author(s):  
Kevin R. McCarthy ◽  
Akiko Watanabe ◽  
Masayuki Kuraoka ◽  
Khoi T. Do ◽  
Charles E. McGee ◽  
...  
Keyword(s):  
B Cells ◽  
Influenza A ◽  
Memory B Cells ◽  
Influenza A Viruses ◽  
Adult Human ◽  
Group 2 ◽  
Group 1

scholarly journals Viral Factors Important for Efficient Replication of Influenza A Viruses in Cells of the Central Nervous System

2019 ◽  
Vol 93 (11) ◽  
Author(s):  
Jurre Y. Siegers ◽  
Marco W. G. van de Bildt ◽  
Zhanmin Lin ◽  
Lonneke M. Leijten ◽  
Rémon A. M. Lavrijssen ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Influenza A ◽  
H5n1 Virus ◽  
Influenza Viruses ◽  
Virus Infections ◽  
Influenza A Viruses ◽  
Cns Disease ◽  
Efficient Replication ◽  
Hpai H5n1 ◽  
In Cells

ABSTRACTCentral nervous system (CNS) disease is one of the most common extrarespiratory tract complications of influenza A virus infections. Remarkably, zoonotic H5N1 virus infections are more frequently associated with CNS disease than seasonal or pandemic influenza viruses. Little is known about the interaction between influenza A viruses and cells of the CNS; therefore, it is currently unknown which viral factors are important for efficient replication. Here, we determined the replication kinetics of a seasonal, pandemic, zoonotic, and lab-adapted influenza A virus in human neuron-like (SK-N-SH) and astrocyte-like (U87-MG) cells and primary mouse cortex neurons. In general, highly pathogenic avian influenza (HPAI) H5N1 virus replicated most efficiently in all cells, which was associated with efficient attachment and infection. Seasonal H3N2 and to a lesser extent pandemic H1N1 virus replicated in a trypsin-dependent manner in SK-N-SH but not in U87-MG cells. In the absence of trypsin, only HPAI H5N1 and WSN viruses replicated. Removal of the multibasic cleavage site (MBCS) from HPAI H5N1 virus attenuated, but did not abrogate, replication. Taken together, our results showed that the MBCS and, to a lesser extent, the ability to attach are important determinants for efficient replication of HPAI H5N1 virus in cells of the CNS. This suggests that both an alternative hemagglutinin (HA) cleavage mechanism and preference for α-2,3-linked sialic acids allowing efficient attachment contribute to the ability of influenza A viruses to replicate efficiently in cells of the CNS. This study further improves our knowledge on potential viral factors important for the neurotropic potential of influenza A viruses.IMPORTANCECentral nervous system (CNS) disease is one of the most common extrarespiratory tract complications of influenza A virus infections, and the frequency and severity differ between seasonal, pandemic, and zoonotic influenza viruses. However, little is known about the interaction of these viruses with cells of the CNS. Differences among seasonal, pandemic, and zoonotic influenza viruses in replication efficacy in CNS cells,in vitro, suggest that the presence of an alternative HA cleavage mechanism and ability to attach are important viral factors. Identifying these viral factors and detailed knowledge of the interaction between influenza virus and CNS cells are important to prevent and treat this potentially lethal CNS disease.

scholarly journals Divergent Human-Origin Influenza Viruses Detected in Australian Swine Populations

2018 ◽  
Vol 92 (16) ◽  
Author(s):  
Frank Y. K. Wong ◽  
Celeste Donato ◽  
Yi-Mo Deng ◽  
Don Teng ◽  
Naomi Komadina ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
Swine Influenza ◽  
Influenza Viruses ◽  
Antigenic Drift ◽  
Human Origin ◽  
Human Influenza ◽  
Influenza A Viruses ◽  
Data Set ◽  
Antigenic Properties

ABSTRACTGlobal swine populations infected with influenza A viruses pose a persistent pandemic risk. With the exception of a few countries, our understanding of the genetic diversity of swine influenza viruses is limited, hampering control measures and pandemic risk assessment. Here we report the genomic characteristics and evolutionary history of influenza A viruses isolated in Australia from 2012 to 2016 from two geographically isolated swine populations in the states of Queensland and Western Australia. Phylogenetic analysis with an expansive human and swine influenza virus data set comprising >40,000 sequences sampled globally revealed evidence of the pervasive introduction and long-term establishment of gene segments derived from several human influenza viruses of past seasons, including the H1N1/1977, H1N1/1995, H3N2/1968, and H3N2/2003, and the H1N1 2009 pandemic (H1N1pdm09) influenza A viruses, and a genotype that contained gene segments derived from the past three pandemics (1968, reemerged 1977, and 2009). Of the six human-derived gene lineages, only one, comprising two viruses isolated in Queensland during 2012, was closely related to swine viruses detected from other regions, indicating a previously undetected circulation of Australian swine lineages for approximately 3 to 44 years. Although the date of introduction of these lineages into Australian swine populations could not be accurately ascertained, we found evidence of sustained transmission of two lineages in swine from 2012 to 2016. The continued detection of human-origin influenza virus lineages in swine over several decades with little or unpredictable antigenic drift indicates that isolated swine populations can act as antigenic archives of human influenza viruses, raising the risk of reemergence in humans when sufficient susceptible populations arise.IMPORTANCEWe describe the evolutionary origins and antigenic properties of influenza A viruses isolated from two separate Australian swine populations from 2012 to 2016, showing that these viruses are distinct from each other and from those isolated from swine globally. Whole-genome sequencing of virus isolates revealed a high genotypic diversity that had been generated exclusively through the introduction and establishment of human influenza viruses that circulated in past seasons. We detected six reassortants with gene segments derived from human H1N1/H1N1pdm09 and various human H3N2 viruses that circulated during various periods since 1968. We also found that these swine viruses were not related to swine viruses collected elsewhere, indicating independent circulation. The detection of unique lineages and genotypes in Australia suggests that isolated swine populations that are sufficiently large can sustain influenza virus for extensive periods; we show direct evidence of a sustained transmission for at least 4 years between 2012 and 2016.

scholarly journals The evolution of human influenza viruses

2001 ◽  
Vol 356 (1416) ◽  
pp. 1861-1870 ◽  
Author(s):  
Alan J. Hay ◽  
Victoria Gregory ◽  
Alan R. Douglas ◽  
Yi Pu Lin
Keyword(s):  
Influenza A ◽  
Influenza Viruses ◽  
Antigenic Drift ◽  
Influenza B ◽  
Mixed Infections ◽  
Human Influenza ◽  
Influenza A Viruses ◽  
Genetic Reassortment ◽  
Influenza Ah1n1 ◽  
Novel Influenza A

The evolution of influenza viruses results in (i) recurrent annual epidemics of disease that are caused by progressive antigenic drift of influenza A and B viruses due to the mutability of the RNA genome and (ii) infrequent but severe pandemics caused by the emergence of novel influenza A subtypes to which the population has little immunity. The latter characteristic is a consequence of the wide antigenic diversity and peculiar host range of influenza A viruses and the ability of their segmented RNA genomes to undergo frequent genetic reassortment (recombination) during mixed infections. Contrasting features of the evolution of recently circulating influenza AH1N1, AH3N2 and B viruses include the rapid drift of AH3N2 viruses as a single lineage, the slow replacement of successive antigenic variants of AH1N1 viruses and the co–circulation over some 25 years of antigenically and genetically distinct lineages of influenza B viruses. Constant monitoring of changes in the circulating viruses is important for maintaining the efficacy of influenza vaccines in combating disease.

scholarly journals Influenza A Virus Vaccination: Immunity, Protection, and Recent Advances Toward A Universal Vaccine

Vaccines ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 434 ◽  
Author(s):  
Christopher E. Lopez ◽  
Kevin L. Legge
Keyword(s):  
Immune Response ◽  
Influenza Virus ◽  
Virus Infection ◽  
Influenza A ◽  
Influenza Virus Infection ◽  
Influenza Viruses ◽  
Antigenic Drift ◽  
Influenza Vaccines ◽  
Virus Infections ◽  
Universal Vaccine

Influenza virus infections represent a serious public health threat and account for significant morbidity and mortality worldwide due to seasonal epidemics and periodic pandemics. Despite being an important countermeasure to combat influenza virus and being highly efficacious when matched to circulating influenza viruses, current preventative strategies of vaccination against influenza virus often provide incomplete protection due the continuous antigenic drift/shift of circulating strains of influenza virus. Prevention and control of influenza virus infection with vaccines is dependent on the host immune response induced by vaccination and the various vaccine platforms induce different components of the local and systemic immune response. This review focuses on the immune basis of current (inactivated influenza vaccines (IIV) and live attenuated influenza vaccines (LAIV)) as well as novel vaccine platforms against influenza virus. Particular emphasis will be placed on how each platform induces cross-protection against heterologous influenza viruses, as well as how this immunity compares to and contrasts from the “gold standard” of immunity generated by natural influenza virus infection.

scholarly journals Repositioning Drugs on Human Influenza A Viruses Based on a Novel Nuclear Norm Minimization Method

2021 ◽  
Vol 11 ◽  
Author(s):  
Hang Liang ◽  
Li Zhang ◽  
Lina Wang ◽  
Man Gao ◽  
Xiangfeng Meng ◽  
...  
Keyword(s):  
Influenza A ◽  
Chemical Structure ◽  
Cross Validation ◽  
Drug Repositioning ◽  
Influenza Pandemic ◽  
Protein Docking ◽  
Influenza Viruses ◽  
Antigenic Drift ◽  
Nuclear Norm ◽  
Influenza A Viruses

Influenza A viruses, especially H3N2 and H1N1 subtypes, are viruses that often spread among humans and cause influenza pandemic. There have been several big influenza pandemics that have caused millions of human deaths in history, and the threat of influenza viruses to public health is still serious nowadays due to the frequent antigenic drift and antigenic shift events. However, only few effective anti-flu drugs have been developed to date. The high development cost, long research and development time, and drug side effects are the major bottlenecks, which could be relieved by drug repositioning. In this study, we proposed a novel antiviral Drug Repositioning method based on minimizing Matrix Nuclear Norm (DRMNN). Specifically, a virus-drug correlation database consisting of 34 viruses and 205 antiviral drugs was first curated from public databases and published literature. Together with drug similarity on chemical structure and virus sequence similarity, we formulated the drug repositioning problem as a low-rank matrix completion problem, which was solved by minimizing the nuclear norm of a matrix with a few regularization terms. DRMNN was compared with three recent association prediction algorithms. The AUC of DRMNN in the global fivefold cross-validation (fivefold CV) is 0.8661, and the AUC in the local leave-one-out cross-validation (LOOCV) is 0.6929. Experiments have shown that DRMNN is better than other algorithms in predicting which drugs are effective against influenza A virus. With H3N2 as an example, 10 drugs most likely to be effective against H3N2 viruses were listed, among which six drugs were reported, in other literature, to have some effect on the viruses. The protein docking experiments between the chemical structure of the prioritized drugs and viral hemagglutinin protein also provided evidence for the potential of the predicted drugs for the treatment of influenza.

scholarly journals An Intranasal Virus-Like Particle Vaccine Broadly Protects Mice from Multiple Subtypes of Influenza A Virus

mBio ◽  
2015 ◽  
Vol 6 (4) ◽  
Author(s):  
Louis M. Schwartzman ◽  
Andrea L. Cathcart ◽  
Lindsey M. Pujanauski ◽  
Li Qi ◽  
John C. Kash ◽  
...  
Keyword(s):  
Public Health ◽  
Influenza A Virus ◽  
Influenza A ◽  
Influenza Viruses ◽  
Significant Protection ◽  
Virus Infections ◽  
Influenza A Viruses ◽  
Virus Like Particle ◽  
Practical Strategy ◽  
Universal Influenza Vaccine

ABSTRACTInfluenza virus infections are a global public health problem, with a significant impact of morbidity and mortality from both annual epidemics and pandemics. The current strategy for preventing annual influenza is to develop a new vaccine each year against specific circulating virus strains. Because these vaccines are unlikely to protect against an antigenically divergent strain or a new pandemic virus with a novel hemagglutinin (HA) subtype, there is a critical need for vaccines that protect against all influenza A viruses, a so-called “universal” vaccine. Here we show that mice were broadly protected against challenge with a wide variety of lethal influenza A virus infections (94% aggregate survival following vaccination) with a virus-like particle (VLP) vaccine cocktail. The vaccine consisted of a mixture of VLPs individually displaying H1, H3, H5, or H7 HAs, and vaccinated mice showed significant protection following challenge with influenza viruses expressing 1918 H1, 1957 H2, and avian H5, H6, H7, H10, and H11 hemagglutinin subtypes. These experiments suggest a promising and practical strategy for developing a broadly protective “universal” influenza vaccine.IMPORTANCEThe rapid and unpredictable nature of influenza A virus evolution requires new vaccines to be produced annually to match circulating strains. Human infections with influenza viruses derived from animals can cause outbreaks that may be associated with high mortality, and such strains may also adapt to humans to cause a future pandemic. Thus, there is a large public health need to create broadly protective, or “universal,” influenza vaccines that could prevent disease from a wide variety of human and animal influenza A viruses. In this study, a noninfectious virus-like particle (VLP) vaccine was shown to offer significant protection against a variety of influenza A viruses in mice, suggesting a practical strategy to develop a universal influenza vaccine.

scholarly journals Serological studies of influenza viruses in pigs in Great Britain 1991–2

1995 ◽  
Vol 114 (3) ◽  
pp. 511-520 ◽  
Author(s):  
I. H. Brown ◽  
P. A. Harris ◽  
D. J. Alexander
Keyword(s):  
Great Britain ◽  
Influenza A ◽  
H1n1 Virus ◽  
Haemagglutination Inhibition ◽  
Influenza Viruses ◽  
Antigenic Drift ◽  
H3n2 Virus ◽  
Influenza B Virus ◽  
Influenza B ◽  
Influenza A Viruses

SUMMARYSamples from a sow serum bank representative of the pig population of Great Britain collected during 1991–2, were examined for antibodies to influenza A, B and C viruses, using viruses which had been isolated from a variety of hosts. For influenza A viruses there was evidence of the continued circulation of ‘classical swine’ H1N1 virus (26%) seroprevalence), and human H3N2 viruses (39%) which are antigenically most closely-related to A/Port Chalmers/1/73 virus. In addition antibodies were detected to A/swine/England/201635/92 (8%), a strain of H3N2 virus which appears to have arisen by antigenic drift from conventional H3N2 swine strains. Specific antibodies (2%) were detected to an H1N1 virus (A/swine/England/195852/92) related most closely to avian H1N1 strains. In tests with human H1N1 and H3N2 viruses, excluding isolates from pigs, the highest seroprevalence was detected to the prevailing strains from the human population. Serological tests with avian H4 and H10, human H2, equine 1 and 2 influenza A viruses were all negative. Seven pigs seropositive by haemagglutination-inhibition, virus neutralization and immunoblotting assays for antibody to influenza B virus, were randomly distributed geographically suggesting that influenza B viruses may be transmitted to pigs but fail to spread. The seroprevalence to influenza C viruses was 9·9% indicating that these viruses are widespread in pigs. These results provide further evidence that the pig can be infected by a number of influenza viruses, some of which may have significance in the epidemiology of human influenza.

scholarly journals Novel Ranking System for Identifying Efficacious Anti-Influenza Virus PB2 Inhibitors

2015 ◽  
Vol 59 (10) ◽  
pp. 6007-6016 ◽  
Author(s):  
Alice W. Tsai ◽  
Colleen F. McNeil ◽  
Joshua R. Leeman ◽  
Hamilton B. Bennett ◽  
Kwame Nti-Addae ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A Virus ◽  
Influenza A ◽  
Therapeutic Agents ◽  
Influenza Viruses ◽  
Antigenic Drift ◽  
Whole Body ◽  
Infection Model ◽  
Virus Infections

ABSTRACTThrough antigenic drift and shifts, influenza virus infections continue to be an annual cause of morbidity in healthy populations and of death among elderly and at-risk patients. The emergence of highly pathogenic avian influenza viruses such as H5N1 and H7N9 and the rapid spread of the swine-origin H1N1 influenza virus in 2009 demonstrate the continued need for effective therapeutic agents for influenza. While several neuraminidase inhibitors have been developed for the treatment of influenza virus infections, these have shown a limited window for treatment initiation, and resistant variants have been noted in the population. In addition, an older class of antiviral drugs for influenza, the adamantanes, are no longer recommended for treatment due to widespread resistance. There remains a need for new influenza therapeutic agents with improved efficacy as well as an expanded window for the initiation of treatment. Azaindole compounds targeting the influenza A virus PB2 protein and demonstrating excellentin vitroandin vivoproperties have been identified. To evaluate thein vivoefficacy of these PB2 inhibitors, we utilized a mouse influenza A virus infection model. In addition to traditional endpoints, i.e., death, morbidity, and body weight loss, we measured lung function using whole-body plethysmography, and we used these data to develop a composite efficacy score that takes compound exposure into account. This model allowed the rapid identification and ranking of molecules relative to each other and to oseltamivir. The ability to identify compounds with enhanced preclinical properties provides an opportunity to develop more-effective treatments for influenza in patients.

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