scholarly journals Mucosal Immunity against Neuraminidase Prevents Influenza B Virus Transmission in Guinea Pigs

mBio ◽  
2019 ◽  
Vol 10 (3) ◽  
Author(s):  
Meagan McMahon ◽  
Ericka Kirkpatrick ◽  
Daniel Stadlbauer ◽  
Shirin Strohmeier ◽  
Nicole M. Bouvier ◽  
...  

ABSTRACTDespite efforts to control influenza virus infection and transmission, influenza viruses still cause significant morbidity and mortality in the global human population each year. Most of the current vaccines target the immunodominant hemagglutinin surface glycoprotein of the virus. However, reduced severity of disease and viral shedding have also been linked to antibodies targeting the second viral surface glycoprotein, the neuraminidase. Importantly, antineuraminidase immunity was shown to be relatively broad, in contrast to vaccine-induced antibodies to the hemagglutinin head domain. In this study, we assessed recombinant neuraminidase protein vaccination for its ability to prevent or limit virus transmission. We vaccinated guinea pigs either intramuscularly or intranasally with a recombinant influenza B virus neuraminidase to assess whether neuraminidase vaccination via these routes could prevent transmission of the homologous virus to a naive recipient. Guinea pigs vaccinated with neuraminidase showed reduced virus titers; however, only vaccination via the intranasal route fully prevented virus transmission to naive animals. We found high levels of antineuraminidase antibodies capable of inhibiting neuraminidase enzymatic activity in the nasal washes of intranasally vaccinated animals, which may explain the observed differences in transmission. We also determined that mucosal immunity to neuraminidase impaired the transmission efficiency of a heterologous influenza B virus, although to a lesser extent. Finally, we found that neuraminidase-vaccinated animals were still susceptible to infection via the airborne and contact transmission routes. However, significantly lower virus titers were detected in these vaccinated recipients. In summary, our data suggest that supplementing vaccine formulations with neuraminidase and vaccinating via the intranasal route may broadly prevent transmission of influenza B viruses.IMPORTANCERecently, the protective effect of anti-neuraminidase immunity has been highlighted by several studies in humans and animal models. However, so far the role that anti-neuraminidase immunity plays in inhibition of virus transmission has not been explored. In addition, neuraminidase has been ignored as an antigen for influenza virus vaccines. We show here that neuraminidase-based vaccines can inhibit the transmission of influenza virus. Therefore, neuraminidase should be considered as an antigen for improved influenza virus vaccines that not only protect individuals from disease but also inhibit further spread of the virus in the population.

1978 ◽  
Vol 80 (1) ◽  
pp. 13-19 ◽  
Author(s):  
N. Masurel ◽  
J. I. de Bruijne ◽  
H. A. Beuningh ◽  
H. J. A. Schouten

SUMMARYHaemagglutination inhibition (HI) antibodies against the influenza viruses A/Hong Kong/8/68 (H3N2) and B/Nederland/77/66 were determined in 420 paired sera from mothers and newborns (umbilical cord sera), sampled in 1970–1.A higher concentration of antibodies against influenza A virus was found more frequently in neonatal than in maternal sera. By contrast, low titres against influenza B virus were more frequently observed in neonatal than in maternal sera. Maternal age, duration of pregnancy, and birth-weight did not affect the results of the tests.It is suggested that the titre of the newborn against an epidemic influenza virus can be predicted from that of the mother. Furthermore, the maternal titre may be an indication of the susceptibility of the newborn infant to influenza infections.


2020 ◽  
pp. 153537022096379
Author(s):  
Oraphan Mayuramart ◽  
Pattaraporn Nimsamer ◽  
Somruthai Rattanaburi ◽  
Naphat Chantaravisoot ◽  
Kritsada Khongnomnan ◽  
...  

Due to the common symptoms of COVID-19, patients are similar to influenza-like illness. Therefore, the detection method would be crucial to discriminate between SARS-CoV-2 and influenza virus-infected patients. In this study, CRISPR-Cas12a-based detection was applied for detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza A virus, and influenza B virus which would be a practical and attractive application for screening of patients with COVID-19 and influenza in areas with limited resources. The limit of detection for SARS-CoV-2, influenza A, and influenza B detection was 10, 103, and 103 copies/reaction, respectively. Moreover, the assays yielded no cross-reactivity against other respiratory viruses. The results revealed that the detection of influenza virus and SARS-CoV-2 by using RT-RPA and CRISPR-Cas12a technology reaches 96.23% sensitivity and 100% specificity for SARS-CoV-2 detection. The sensitivity for influenza virus A and B detections was 85.07% and 94.87%, respectively. In addition, the specificity for influenza virus A and B detections was approximately 96%. In conclusion, the RT-RPA with CRISPR-Cas12a assay was an effective method for the screening of influenza viruses and SARS-CoV-2 which could be applied to detect other infectious diseases in the future.


PEDIATRICS ◽  
1991 ◽  
Vol 88 (5) ◽  
pp. 1031-1036
Author(s):  
Roland A. Levandowski ◽  
Helen L. Regnery ◽  
Eldridge Staton ◽  
B. Gail Burgess ◽  
Michael S. Williams ◽  
...  

The cocirculation in several parts of the world of influenza viruses B/Yamagata/16/88 and B/Victoria/2/87, which are genetically and antigenically divergent, has prompted the question of whether immunization with one viral antigen is sufficient for protection against both strains. Twenty-three high-risk infants and young children were immunized with a commercial trivalent influenza vaccine containing the antigens of influenza virus B/Yamagata/16/88. When antibodies against influenza viruses B/Yamagata/16/88 and B/Victoria/2/87 were determined, increases developed uniformly to both in the sera of primed children previously exposed to influenza virus B/Victoria/2/87 by immunization or infection. Antibodies against B/Yamagata/16/88 developed in the sera of unprimed children with titers similar to those of the primed children. However, antibodies to B/ Victoria/2/87 were not detected in the sera of the unprimed children. These data suggest that children with out appropriate immunologic priming may not be protected against an infection with a B/Victoria/2/87 strain after vaccination with a B/Yamagata/16/88 strain. Immunization with more than one influenza B virus strain may be desirable in some high-risk pediatric patients if divergent influenza B viruses circulate.


1947 ◽  
Vol 86 (2) ◽  
pp. 125-129 ◽  
Author(s):  
C. A. Knight

Microbiological assays for amino acids were made on hydrolysates of four to five highly purified preparations each of influenza A virus (PR8 strain) and influenza B virus (Lee strain). The results of the assays indicated that these strains of influenza virus contain approximately the same amounts of alanine, aspartic acid, glycine, histidine, isoleucine, leucine, methionine, phenylalanine, proline, serine, threonine, and valine. However, significant differences were found in the values for arginine, glutamic acid, lysine, tryptophane, and tyrosine. It is believed that these differences may provide, at least in part, a chemical explanation for some of the differing properties of the PR8 and Lee strains of influenza viruses.


2021 ◽  
Vol 12 ◽  
Author(s):  
Yonghong Liu ◽  
Shirin Strohmeier ◽  
Irene González-Domínguez ◽  
Jessica Tan ◽  
Viviana Simon ◽  
...  

Influenza viruses undergo antigenic changes in the immuno-dominant hemagglutinin (HA) head domain, necessitating annual re-formulation of and re-vaccination with seasonal influenza virus vaccines for continuing protection. We previously synthesized mosaic HA (mHA) proteins of influenza B viruses which redirect the immune response towards the immuno-subdominant conserved epitopes of the HA via sequential immunization. As ~90% of current influenza virus vaccines are manufactured using the inactivated virus platform, we generated and sequentially vaccinated mice with inactivated influenza B viruses displaying either the homologous (same B HA backbones) or the heterologous (different B HA backbones) mosaic HAs. Both approaches induced long-lasting and cross-protective antibody responses showing strong antibody-dependent cellular cytotoxicity (ADCC) activity. We believe the B virus mHA vaccine candidates represent a major step towards a universal influenza B virus vaccine.


1998 ◽  
Vol 36 (6) ◽  
pp. 1544-1548 ◽  
Author(s):  
Shimian Zou ◽  
Carol Stansfield ◽  
Jodi Bridge

A quick genetic approach for the screening of influenza virus variants was developed in this laboratory (S. Zou, J. Clin. Microbiol. 35:2623–2627, 1997). It uses multiplex reverse transcription and multiplex PCR to amplify and differentiate the variable region of the hemagglutinin genes of different types and subtypes of influenza viruses. Variants within the same type or subtype are then identified by the heteroduplex mobility shift assay of the amplicons. The method was used to screen influenza virus isolates received from provincial laboratories during the 1996–1997 season and was able to identify new influenza B virus variants. Sequencing of the amplicons derived from the hemagglutinin gene of the identified variants and comparison with the vaccine strain B/Harbin/7/94 showed substitution rates of 2.26 to 2.55% at the nucleotide level and 4.26 to 4.68% at the amino acid level. The result further demonstrated that the approach provides a quick, sensitive, and reliable screening for influenza virus variants. It also suggested the necessity of close monitoring of influenza B virus isolates in the 1997–1998 season and critical evaluation of the reference strain for the type B influenza virus.


Author(s):  
Pınar YAZICI ÖZKAYA ◽  
Eşe Eda TURANLI ◽  
Hamdi METİN ◽  
Ayça Aydın UYSAL ◽  
Candan ÇİÇEK ◽  
...  

Folia Medica ◽  
2015 ◽  
Vol 57 (2) ◽  
pp. 104-110 ◽  
Author(s):  
Golubinka Bosevska ◽  
Nikola Panovski ◽  
Elizabeta Janceska ◽  
Vladimir Mikik ◽  
Irena Kondova Topuzovska ◽  
...  

AbstractEarly diagnosis and treatment of patients with influenza is the reason why physicians need rapid high-sensitivity influenza diagnostic tests that require no complex lab equipment and can be performed and interpreted within 15 min. The Aim of this study was to compare the rapid Directigen Flu A+B test with real time PCR for detection of influenza viruses in the Republic of Macedonia. MATERIALS AND METHODS: One-hundred-eight respiratory samples (combined nose and throat swabs) were routinely collected for detection of influenza virus during influenza seasons. Forty-one patients were pediatric cases and 59 were adult. Their mean age was 23 years. The patients were allocated into 6 age groups: 0 - 4 yrs, 5 - 9 yrs, 10 - 14 yrs, 15 - 19 yrs, 20-64 yrs and > 65 yrs. Each sample was tested with Directigen Flu A+B and CDC real time PCR kit for detection and typisation/subtypisation of influenza according to the lab diagnostic protocol. RESULTS: Directigen Flu A+B identified influenza A virus in 20 (18.5%) samples and influenza B virus in two 2 (1.9%) samples. The high specificity (100%) and PPV of Directigen Flu A+B we found in our study shows that the positive results do not need to be confirmed. The overall sensitivity of Directigen Flu A+B is 35.1% for influenza A virus and 33.0% for influenza B virus. The sensitivity for influenza A is higher among children hospitalized (45.0%) and outpatients (40.0%) versus adults. CONCLUSION: Directigen Flu A+B has relatively low sensitivity for detection of influenza viruses in combined nose and throat swabs. Negative results must be confirmed.


2014 ◽  
Vol 66 (1) ◽  
pp. 43-50 ◽  
Author(s):  
J. Radovanov ◽  
V. Milosevic ◽  
I. Hrnjakovic ◽  
V. Petrovic ◽  
M. Ristic ◽  
...  

At present, two influenza A viruses, H1N1pdm09 and H3N2, along with influenza B virus co-circulate in the human population, causing endemic and seasonal epidemic acute febrile respiratory infections, sometimes with life-threatening complications. Detection of influenza viruses in nasopharyngeal swab samples was done by real-time RT-PCR. There were 60.2% (53/88) positive samples in 2010/11, 63.4% (52/82) in 2011/12, and 49.9% (184/369) in 2012/13. Among the positive patients, influenza A viruses were predominant during the first two seasons, while influenza B type was more active during 2012/13. Subtyping of influenza A positive samples revealed the presence of A (H1N1)pdm09 in 2010/11, A (H3N2) in 2011/12, while in 2012/13, both subtypes were detected. The highest seroprevalence against influenza A was in the age-group 30-64, and against influenza B in adults aged 30-64 and >65.


mBio ◽  
2018 ◽  
Vol 9 (2) ◽  
Author(s):  
Mira C. Patel ◽  
Kari Ann Shirey ◽  
Marina S. Boukhvalova ◽  
Stefanie N. Vogel ◽  
Jorge C. G. Blanco

ABSTRACT Host-derived “danger-associated molecular patterns” (DAMPs) contribute to innate immune responses and serve as markers of disease progression and severity for inflammatory and infectious diseases. There is accumulating evidence that generation of DAMPs such as oxidized phospholipids and high-mobility-group box 1 (HMGB1) during influenza virus infection leads to acute lung injury (ALI). Treatment of influenza virus-infected mice and cotton rats with the Toll-like receptor 4 (TLR4) antagonist Eritoran blocked DAMP accumulation and ameliorated influenza virus-induced ALI. However, changes in systemic HMGB1 kinetics during the course of influenza virus infection in animal models and humans have yet to establish an association of HMGB1 release with influenza virus infection. To this end, we used the cotton rat model that is permissive to nonadapted strains of influenza A and B viruses, respiratory syncytial virus (RSV), and human rhinoviruses (HRVs). Serum HMGB1 levels were measured by an enzyme-linked immunosorbent assay (ELISA) prior to infection until day 14 or 18 post-infection. Infection with either influenza A or B virus resulted in a robust increase in serum HMGB1 levels that decreased by days 14 to 18. Inoculation with the live attenuated vaccine FluMist resulted in HMGB1 levels that were significantly lower than those with infection with live influenza viruses. RSV and HRVs showed profiles of serum HMGB1 induction that were consistent with their replication and degree of lung pathology in cotton rats. We further showed that therapeutic treatment with Eritoran of cotton rats infected with influenza B virus significantly blunted serum HMGB1 levels and improved lung pathology, without inhibiting virus replication. These findings support the use of drugs that block HMGB1 to combat influenza virus-induced ALI. IMPORTANCE Influenza virus is a common infectious agent causing serious seasonal epidemics, and there is urgent need to develop an alternative treatment modality for influenza virus infection. Recently, host-derived DAMPs, such as oxidized phospholipids and HMGB1, were shown to be generated during influenza virus infection and cause ALI. To establish a clear link between influenza virus infection and HMGB1 as a biomarker, we have systematically analyzed temporal patterns of serum HMGB1 release in cotton rats infected with nonadapted strains of influenza A and B viruses and compared these patterns with a live attenuated influenza vaccine and infection by other respiratory viruses. Towards development of a new therapeutic modality, we show herein that blocking serum HMGB1 levels by Eritoran improves lung pathology in influenza B virus-infected cotton rats. Our study is the first report of systemic HMGB1 as a potential biomarker of severity in respiratory virus infections and confirms that drugs that block virus-induced HMGB1 ameliorate ALI.


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