Monoclonal Antibody Therapy Protects Pharmacologically Immunosuppressed Mice from Lethal Infection with Influenza B Virus

ABSTRACT Human influenza A and B viruses are highly contagious and cause similar illnesses and seasonal epidemics. Currently available antiviral drugs have limited efficacy in humans with compromised immune systems; therefore, alternative strategies for protection are needed. Here, we investigated whether monoclonal antibodies (MAbs) targeting hemagglutinin (HA) and/or neuraminidase (NA) proteins would protect immunosuppressed mice from severe infections with influenza B virus. Pharmacologically immunosuppressed BALB/c mice were inoculated with B/Brisbane/60/2008 (BR/08) influenza virus and were treated with a single dose of 1, 5, or 25 mg/kg of body weight per day of either an anti-HA MAb (1D2) or an anti-NA MAb (1F2) starting at 24 hours postinoculation (hpi). Monotherapy with 1D2 or 1F2 MAbs provided dose-dependent protection of mice, with decreased BR/08 virus replication and spread in the mouse lungs, compared with those of controls. Combination treatment with 1D2 and 1F2 provided greater protection than did monotherapy, even when started at 48 hpi. Virus spread was also efficiently restrained within the lungs, being limited to 6%, 10%, and 10% of that seen in active infection when treatment was initiated at 24, 48, and 72 hpi, respectively. In most cases, the expression of cytokines and chemokines was altered according to when treatment was initiated. Higher expression of proinflammatory IP-10 and MCP-1 in combination-treatment groups, but not in monotherapy groups, to some extent, promoted better control of virus spread within the lungs. This study demonstrates the potential value of MAb immunotherapy in treating influenza in immunocompromised hosts who are at increased risk of severe disease.

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Severe Influenza Virus Infection in Children Admitted to the PICU: Comparison of Influenza A and Influenza B Virus Infection

Journal of Medical Virology ◽

10.1002/jmv.27400 ◽

2021 ◽

Author(s):

Pınar YAZICI ÖZKAYA ◽

Eşe Eda TURANLI ◽

Hamdi METİN ◽

Ayça Aydın UYSAL ◽

Candan ÇİÇEK ◽

...

Keyword(s):

Influenza Virus ◽

Virus Infection ◽

Influenza A ◽

Influenza Virus Infection ◽

Influenza B Virus ◽

Influenza B ◽

Severe Influenza ◽

B Virus

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Clinical Investigations. Comparison of Directigen Flu A+B with Real Time PCR in the Diagnosis of Influenza / Сравнение Иммунохроматографического Метода (Directigen Flu A+B) И Теста RT-PCR При Инфекциях Гриппа

Folia Medica ◽

10.1515/folmed-2015-0027 ◽

2015 ◽

Vol 57 (2) ◽

pp. 104-110 ◽

Cited By ~ 4

Author(s):

Golubinka Bosevska ◽

Nikola Panovski ◽

Elizabeta Janceska ◽

Vladimir Mikik ◽

Irena Kondova Topuzovska ◽

...

Keyword(s):

Real Time ◽

Influenza A Virus ◽

Real Time Pcr ◽

Influenza A ◽

Age Groups ◽

Influenza Viruses ◽

Influenza B Virus ◽

Influenza B ◽

B Virus ◽

Nose And Throat

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.

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Haemagglutination-inhibition antibodies against influenza A and influenza B in maternal and neonatal sera

Journal of Hygiene ◽

10.1017/s0022172400053353 ◽

1978 ◽

Vol 80 (1) ◽

pp. 13-19 ◽

Cited By ~ 6

Author(s):

N. Masurel ◽

J. I. de Bruijne ◽

H. A. Beuningh ◽

H. J. A. Schouten

Keyword(s):

Influenza Virus ◽

Maternal Age ◽

Influenza A ◽

Haemagglutination Inhibition ◽

Influenza Viruses ◽

Influenza B Virus ◽

Influenza B ◽

B Virus ◽

Duration Of Pregnancy ◽

Pregnancy And Birth

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.

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Influenza A and B viruses in the population of Vojvodina, Serbia

Archives of Biological Sciences ◽

10.2298/abs1401043r ◽

2014 ◽

Vol 66 (1) ◽

pp. 43-50 ◽

Cited By ~ 2

Author(s):

J. Radovanov ◽

V. Milosevic ◽

I. Hrnjakovic ◽

V. Petrovic ◽

M. Ristic ◽

...

Keyword(s):

Influenza A ◽

Respiratory Infections ◽

Influenza Viruses ◽

Influenza B Virus ◽

Nasopharyngeal Swab ◽

Influenza B ◽

Influenza A Viruses ◽

B Virus ◽

Life Threatening ◽

Seasonal Epidemic

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.

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Epidemiological and virological assessment of influenza activity in Europe during the winter 2005-2006

Eurosurveillance ◽

10.2807/esm.12.09.00733-en ◽

2007 ◽

Vol 12 (9) ◽

pp. 11-12 ◽

Cited By ~ 15

Author(s):

A Meijer ◽

T J Meerhoff ◽

L. E. Meuwissen ◽

J Van Der Velden ◽

W J Paget ◽

...

Keyword(s):

Influenza A ◽

New Caledonia ◽

Influenza B Virus ◽

Random Pattern ◽

Clinical Activity ◽

Influenza B ◽

Influenza A Viruses ◽

B Virus ◽

Influenza Activity ◽

Spread Pattern

Influenza activity in Europe during the winter 2005-2006 started late January - early February 2006 and first occurred in the Netherlands, France, Greece and England. Subsequently, countries were affected in a random pattern across Europe and the period of influenza activity lasted till the end of April. In contrast to the winter seasons in the period 2001-2005, no west-east pattern was detected. In 12 out of 23 countries, the consultation rates for influenza-like illness or acute respiratory infection in the winter 2005-2006 were similar or higher than in the winter 2004-2005, despite a dominance of influenza B viruses that normally cause milder disease than influenza A viruses. In the remaining 11 countries the consultation rates were lower to much lower than in the winter 2004-2005. The highest consultation rates were usually observed among children aged 0-14. The circulating influenza virus types and subtypes were distributed heterogeneously across Europe. Although the figures for total virus detections in Europe indicated a predominance of influenza B virus (58% of all virus detections), in many countries influenza B virus was predominant only early in the winter, whilst later there was a marked increase in influenza A virus detections. Among the countries where influenza A viruses were co-dominant with B viruses (9/29) or were predominant (4/29), the dominant influenza A subtype was H3 in seven countries and H1 in four countries. The vast majority of characterised influenza B viruses (90%) were similar to the B/Victoria/2/87 lineage of influenza B viruses that re-emerged in Europe in the winter 2004-2005 but were not included in the vaccine for the influenza season 2005-2006. This might help to explain the dominance of influenza B viruses in many countries in Europe during the winter 2005-2006. The influenza A(H3) and A(H1) viruses were similar to the reference strains included in the 2005-2006 vaccine, A/California/7/2004 (H3N2) and A/New Caledonia/20/99 (H1N1), respectively. In conclusion, the 2005-2006 influenza epidemic in Europe was characterised by moderate clinical activity, a heterogeneous spread pattern across Europe, and a variable virus dominance by country, although an overall dominance of influenza B viruses that did not match the virus strain included in the vaccine was observed.

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Serum High-Mobility-Group Box 1 as a Biomarker and a Therapeutic Target during Respiratory Virus Infections

mBio ◽

10.1128/mbio.00246-18 ◽

2018 ◽

Vol 9 (2) ◽

Cited By ~ 16

Author(s):

Mira C. Patel ◽

Kari Ann Shirey ◽

Marina S. Boukhvalova ◽

Stefanie N. Vogel ◽

Jorge C. G. Blanco

Keyword(s):

Influenza Virus ◽

Virus Infection ◽

Influenza A ◽

Influenza Virus Infection ◽

High Mobility ◽

Influenza B Virus ◽

Influenza B ◽

Lung Pathology ◽

B Virus ◽

Cotton Rats

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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The importance of distinguishing COVID-19 from more common respiratory illnesses

Epidemiology and Infection ◽

10.1017/s0950268820001971 ◽

2020 ◽

Vol 148 ◽

Author(s):

Wei Zhao ◽

Xingzhi Xie ◽

Jun Liu

Keyword(s):

Computed Tomography ◽

Influenza A ◽

Influenza B Virus ◽

Influenza B ◽

Imaging Findings ◽

Influenza A Viruses ◽

Respiratory Illnesses ◽

B Virus ◽

Virus Pneumonia

Abstract We recruited 1591 patients who presented to our fever clinics from 23 January 2020 to 16 February 2020. The different imaging findings between COVID-19 pneumonia and influenza A viruses, influenza B virus pneumonia were also investigated. Most patients were infected by influenza A and B viruses in the flu-season. A laboratory kit is urgently needed to test different viruses simultaneously. Computed tomography can help early screen suspected patients with COVID-19 and differentiate different virus-related pneumonia.

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Detection of severe acute respiratory syndrome coronavirus 2 and influenza viruses based on CRISPR-Cas12a

Experimental Biology and Medicine ◽

10.1177/1535370220963793 ◽

2020 ◽

pp. 153537022096379

Author(s):

Oraphan Mayuramart ◽

Pattaraporn Nimsamer ◽

Somruthai Rattanaburi ◽

Naphat Chantaravisoot ◽

Kritsada Khongnomnan ◽

...

Keyword(s):

Influenza Virus ◽

Severe Acute Respiratory Syndrome ◽

Influenza A ◽

Limit Of Detection ◽

Cross Reactivity ◽

Influenza Viruses ◽

Influenza B Virus ◽

Influenza B ◽

Influenza Virus A ◽

B Virus

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.

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Co-circulation of the two influenza B lineages during 13 consecutive influenza surveillance seasons in Italy, 2004–2017

BMC Infectious Diseases ◽

10.1186/s12879-019-4621-z ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 6

Author(s):

Simona Puzelli ◽

◽

Angela Di Martino ◽

Marzia Facchini ◽

Concetta Fabiani ◽

...

Keyword(s):

Influenza A ◽

Respiratory Illness ◽

Influenza Surveillance ◽

Influenza B Virus ◽

Influenza B ◽

Virus Infections ◽

Ha Gene ◽

B Virus ◽

B Lineage ◽

Trivalent Vaccine

Abstract Background Since 1985, two antigenically distinct lineages of influenza B viruses (Victoria-like and Yamagata-like) have circulated globally. Trivalent seasonal influenza vaccines contain two circulating influenza A strains but a single B strain and thus provide limited immunity against circulating B strains of the lineage not included in the vaccine. In this study, we describe the characteristics of influenza B viruses that caused respiratory illness in the population in Italy over 13 consecutive seasons of virological surveillance, and the match between the predominant influenza B lineage and the vaccine B lineage, in each season. Methods From 2004 to 2017, 26,886 laboratory-confirmed influenza cases were registered in Italy, of which 18.7% were type B. Among them, the lineage of 2465 strains (49%) was retrieved or characterized in this study by a real-time RT-PCR assay and/or sequencing of the hemagglutinin (HA) gene. Results Co-circulation of both B lineages was observed each season, although in different proportions every year. Overall, viruses of B/Victoria and B/Yamagata lineages caused 53.3 and 46.7% of influenza B infections, respectively. A higher proportion of infections with both lineages was detected in children, and there was a declining frequency of B/Victoria detections with age. A mismatch between the vaccine and the predominant influenza B lineage occurred in eight out of thirteen influenza seasons under study. Considering the seasons when B accounted for > 20% of all laboratory-confirmed influenza cases, a mismatch was observed in four out of six seasons. Phylogenetic analysis of the HA1 domain confirmed the co-circulation of both lineages and revealed a mixed circulation of distinct evolutionary viral variants, with different levels of match to the vaccine strains. Conclusions This study contributes to the understanding of the circulation of influenza B viruses in Italy. We found a continuous co-circulation of both B lineages in the period 2004–2017, and determined that children were particularly vulnerable to Victoria-lineage influenza B virus infections. An influenza B lineage mismatch with the trivalent vaccine occurred in about two-thirds of cases.

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Comparative Outcomes of Adults Hospitalized With Seasonal Influenza A or B Virus Infection: Application of the 7-Category Ordinal Scale

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz053 ◽

2019 ◽

Vol 6 (3) ◽

Cited By ~ 7

Author(s):

Yeming Wang ◽

Guohui Fan ◽

Peter Horby ◽

Fredrick Hayden ◽

Qian Li ◽

...

Keyword(s):

Virus Infection ◽

Clinical Improvement ◽

Influenza A ◽

Cox Model ◽

Normal Activity ◽

Ordinal Scale ◽

Influenza B Virus ◽

Influenza B ◽

B Virus ◽

The Difference

Abstract Background The objective of this study was to investigate the difference in disease severity between influenza A and B among hospitalized adults using a novel ordinal scale and existing clinical outcome end points. Methods A prospective, observational study was conducted over the 2016–2018 influenza seasons in a central hospital. The primary outcome was the rate of clinical improvement, defined as a decline of 2 categories from admission on a 7-category ordinal scale that ranges from 1 (discharged with normal activity) to 7 (death), or hospital discharge up to day 28. Results In total, 574 eligible patients were enrolled, including 369 (64.3%) influenza A cases and 205 (35.7%) influenza B cases. The proportion of patients with a worse ordinal scale at admission was higher in influenza A than influenza B (P = .0005). Clinical improvement up to 28 days occurred in 82.4% of patients with influenza A and 90.7% of patients with influenza B (P = .0067). The Cox model indicated that influenza B patients had a higher clinical improvement probability than influenza A cases (adjusted hazard ratio [HR], 1.266; 95% confidence interval [CI], 1.019–1.573; P = .0335). A similar pattern was observed in weaning oxygen supplement (adjusted HR, 1.285; 95% CI, 1.030–1.603; P = .0261). In-hospital mortality for influenza A was marginally higher than influenza B (11.4% vs 6.8%; P = .0782). Conclusions Our findings indicated that hospitalized patients with influenza A were more ill and had delayed clinical improvement compared with those with influenza B virus infection.

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