scholarly journals Antibody Responses toward the Major Antigenic Sites of Influenza B Virus Hemagglutinin in Mice, Ferrets, and Humans

2018 ◽  
Vol 93 (2) ◽  
Author(s):  
Weina Sun ◽  
Davina S. Kang ◽  
Allen Zheng ◽  
Sean T. H. Liu ◽  
Felix Broecker ◽  
...  

ABSTRACTThe influenza B virus hemagglutinin contains four major antigenic sites (the 120 loop, the 150 loop, the 160 loop, and the 190 helix) within the head domain. These immunodominant antigenic sites are the main targets of neutralizing antibodies and are subject to antigenic drift. Yet little is known about the specific antibody responses toward each site in terms of antibody prevalence and hemagglutination inhibition activity. In this study, we used modified hemagglutinins of influenza B virus which display only one or none of the major antigenic sites to measure antibody responses toward the classical as well as the noncanonical epitopes in mice, ferrets, and humans. With our novel reagents, we found that both hemagglutination inhibition antibodies and total IgGs were mostly induced by the major antigenic sites. However, in human adults, we observed high hemagglutination inhibition antibody responses toward the noncanonical epitopes. By stratifying the human samples into age groups, we found that the noncanonical antibody responses appeared to increase with age.IMPORTANCEThis study dissected the specific antibody responses toward the major antigenic sites and the noncanonical epitopes of influenza B virus hemagglutinin in animals and humans using novel reagents. These findings will guide the design of the next generation of influenza virus vaccines.

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.


Author(s):  
Ewelina Hallmann-Szelińska ◽  
Karol Szymański ◽  
Katarzyna Łuniewska ◽  
Katarzyna Kondratiuk ◽  
Lidia Bernadeta Brydak

The aim of this study was to determine the level of antibodies against hemagglutinin of influenza viruses in the sera of people in the seven age groups in the epidemic season 2018/2019 in Poland. The level of anti-hemagglutinin antibodies was determined by hemagglutination inhibition test (HAI). 1050 clinical samples from all over the country were tested. The level of antibodies against influenza viruses was highest in the 10–14 age group for A/Singapore/INFIMH-16-0019/2016 (H3N2) and B/Phuket/3073/2013 Yamagata lineage antigens. These results confirm the circulation of four antigenically different influenza virus strains, two subtypes of influenza A virus – A/Michigan/45/2015 (H1N1)pdm09 and A/Singapore/INFIMH-16-0019/2016 (H3N2) and two lineages of influenza B virus – B/Colorado/06/2017 – Victoria lineage and B/Phuket/3073/2013 Yamagata lineage.


2020 ◽  
Vol 36 (3) ◽  
Author(s):  
Cácia Régia  De Paula ◽  
Eliane Lemes  De Morais ◽  
Patrícia de Sá  Barros ◽  
Ludmila Grego  Maia ◽  
Bruno Bordin  Pelazza ◽  
...  

The influenza B virus is more stable than influenza A, with less antigenic drift and consequent immunologic stability, and does not undergo the process of antigenic shift, its participation in epidemics is minimal, being of lesser academic interest. The aim of this work was to describe the occurrence of a series of SARS cases in a municipality in the Central region of Brazil. This is a case series study with a descriptive and quantitative approach of Serious Acute Respiratory Syndrome (SARS) in institutionalized individuals and a health professional from a long-term institution in the municipality where the study was conducted. The variables studied were: age, comorbidities, vaccination status, date of symptoms onset, symptoms, occurrence of death, information regarding provided care (hospital care, exams, and medications). The study was approved by the Research Ethics Committee of the Federal University of Goiás (UFG), under opinion number 2.167.287. Case 1 was diagnosed with influenza B, treated with antibiotic therapy, with no antiviral drugs administered, and culminated in death. Cases 2 and 3 were confirmed as influenza B, being treated with antiviral drugs and discharged due to full recovery. Case 4 was confirmed as influenza B virus by epidemiological link, treated with antiviral drugs and discharged due to full recovery. An early diagnosis, adequate clinical management, transmissible disease research based on the 11 health promotion steps and actions can promote the reduction of morbimortality by influenza type B.


1998 ◽  
Vol 72 (5) ◽  
pp. 4472-4477 ◽  
Author(s):  
I. V. Alymova ◽  
S. Kodihalli ◽  
E. A. Govorkova ◽  
B. Fanget ◽  
C. Gerdil ◽  
...  

ABSTRACT The immunogenicity and protective efficacy of formalin-inactivated influenza B/Memphis/1/93 virus vaccines propagated exclusively in Vero cells, MDCK cells, or embryonated chicken eggs (hereafter referred to as eggs) were investigated. Mammalian cell-grown viruses differ from the egg-grown variant at amino acid position 198 (Pro/Thr) in the hemagglutinin gene. The level of neuraminidase activity was highest in egg-grown virus, while MDCK and Vero cell-derived viruses possessed 70 and 90% less activity, respectively. After boosting, each of the vaccines induced high levels of hemagglutinin-inhibiting, neuraminidase-inhibiting, and neutralizing antibodies that provided complete protection from MDCK-grown virus challenge. Mammalian cell-derived virus vaccines induced serum antibodies that were more cross-reactive, while those induced by egg-grown virus vaccines were more specific to the homologous antigen. Enzyme-linked immunospot analysis indicated that cell-grown virus vaccines induced high frequencies of immunoglobulin G (IgG)-producing cells directed against both cell- and egg-grown virus antigens, whereas egg-grown virus vaccine induced higher frequencies of IgG- and IgM-producing cells reacting with homologous antigen and low levels of IgG-producing cells reactive with cell-grown viruses. These studies indicate that influenza B virus variants selected in different host systems can elicit different immune responses, but these alterations had no detectable influence on the protective efficacy of the vaccines with the immunization protocol used in this study.


2015 ◽  
Vol 89 (23) ◽  
pp. 12226-12231 ◽  
Author(s):  
Benjamin O. Fulton ◽  
Peter Palese ◽  
Nicholas S. Heaton

Influenza B virus is a human pathogen responsible for significant health and economic burden. Research into this pathogen has been limited by the lack of reporter viruses. Here we describe the development of both a replication-competent fluorescent influenza B reporter virus and bioluminescent influenza B reporter virus. Furthermore, we demonstrate these reporter viruses can be used to quickly monitor viral growth and permit the rapid screening of antiviral compounds and neutralizing antibodies.


2017 ◽  
Vol 91 (12) ◽  
Author(s):  
Megan E. Ermler ◽  
Ericka Kirkpatrick ◽  
Weina Sun ◽  
Rong Hai ◽  
Fatima Amanat ◽  
...  

ABSTRACT Seasonal influenza virus epidemics represent a significant public health burden. Approximately 25% of all influenza virus infections are caused by type B viruses, and these infections can be severe, especially in children. Current influenza virus vaccines are an effective prophylaxis against infection but are impacted by rapid antigenic drift, which can lead to mismatches between vaccine strains and circulating strains. Here, we describe a broadly protective vaccine candidate based on chimeric hemagglutinins, consisting of globular head domains from exotic influenza A viruses and stalk domains from influenza B viruses. Sequential vaccination with these constructs in mice leads to the induction of broadly reactive antibodies that bind to the conserved stalk domain of influenza B virus hemagglutinin. Vaccinated mice are protected from lethal challenge with diverse influenza B viruses. Results from serum transfer experiments and antibody-dependent cell-mediated cytotoxicity (ADCC) assays indicate that this protection is antibody mediated and based on Fc effector functions. The present data suggest that chimeric hemagglutinin-based vaccination is a viable strategy to broadly protect against influenza B virus infection. IMPORTANCE While current influenza virus vaccines are effective, they are affected by mismatches between vaccine strains and circulating strains. Furthermore, the antiviral drug oseltamivir is less effective for treating influenza B virus infections than for treating influenza A virus infections. A vaccine that induces broad and long-lasting protection against influenza B viruses is therefore urgently needed.


1970 ◽  
Vol 68 (2) ◽  
pp. 233-244 ◽  
Author(s):  
Jean C. Downie ◽  
C. H. Stuart-Harris

SUMMARYTrials were made in volunteers in 1967 and 1968 of various virus vaccines against influenza virus B. Sera and serially collected nasal washings before and after immunization were tested respectively for haemagglutination-inhibiting and tissue culture virus-neutralizing antibodies to the same strain of influenza B/Eng/65 virus as that used in the vaccines. Infection, as determined by recovery of virus and serological changes following intranasal instillation of attenuated live virus, was accompanied by the subsequent appearance of neutralizing antibodies in nasal secretion. Inactivated vaccine subcutaneously did not evoke nasal antibody formation in 1967 but did so in 1968.In 1968 intranasal challenge of the volunteers with the attenuated virus 1 month after immunization demonstrated a correlation of susceptibility or resistance to infection with nasal and serum antibodies. Resistance appeared to depend either on a high level of serum antibodies or nasal antibodies, or both.


2018 ◽  
Vol 92 (16) ◽  
Author(s):  
Benjamin O. Fulton ◽  
Weina Sun ◽  
Nicholas S. Heaton ◽  
Peter Palese

ABSTRACTInfluenza A and B viruses can continuously evade humoral immune responses by developing mutations in the globular head of the hemagglutinin (HA) that prevent antibody binding. However, the influenza B virus HA over time displays less antigenic variation despite being functionally and structurally similar to the influenza A virus HA. To determine if the influenza B virus HA is under constraints that limit its antigenic variation, we performed a transposon screen to compare the mutational tolerance of the currently circulating influenza A virus HAs (H1 and H3 subtypes) and influenza B virus HAs (B/Victoria87 and B/Yamagata88 antigenic lineages). A library of insertional mutants for each HA was generated and deep sequenced after passaging to determine where insertions were tolerated in replicating viruses. The head domains of both viruses tolerated transposon mutagenesis, but the influenza A virus head was more tolerant to insertions than the influenza B virus head domain. Furthermore, all five of the known antigenic sites of the influenza A virus HA were tolerant of 15 nucleotide insertions, while insertions were detected in only two of the four antigenic sites in the influenza B virus head domain. Our analysis demonstrated that the influenza B virus HA is inherently less tolerant of transposon-mediated insertions than the influenza A virus HA. The reduced insertional tolerance of the influenza B virus HA may reveal genetic restrictions resulting in a lower capacity for antigenic evolution.IMPORTANCEInfluenza viruses cause seasonal epidemics and result in significant human morbidity and mortality. Influenza viruses persist in the human population through generating mutations in the hemagglutinin head domain that prevent antibody recognition. Despite the similar selective pressures on influenza A and B viruses, influenza A virus displays a higher rate and breadth of antigenic variability than influenza B virus. A transposon mutagenesis screen was used to examine if the reduced antigenic variability of influenza B virus was due to inherent differences in mutational tolerance. This study demonstrates that the influenza A virus head domain and the individual antigenic sites targeted by humoral responses are more tolerant to insertions than those of influenza B virus. This finding sheds light on the genetic factors controlling the antigenic evolution of influenza viruses.


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