scholarly journals Epitope mapping of the 2009 pandemic and the A/Brisbane/59/2007 seasonal (H1N1) influenza virus haemagglutinins using mAbs and escape mutants

2014 ◽  
Vol 95 (11) ◽  
pp. 2377-2389 ◽  
Author(s):  
Miguel Retamal ◽  
Yacine Abed ◽  
Jacques Corbeil ◽  
Guy Boivin
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
Epitope Mapping ◽  
Antigenic Site ◽  
H1n1 Influenza ◽  
Hek293 Cells ◽  
Antigenic Sites ◽  
Influenza A H1n1 ◽  
Biological Tool ◽  
Escape Mutants

mAbs constitute an important biological tool for influenza virus haemagglutinin (HA) epitope mapping through the generation of escape mutants, which could provide insights into immune evasion mechanisms and may benefit the future development of vaccines. Several influenza A (H1N1) pandemic 2009 (pdm09) HA escape mutants have been recently described. However, the HA antigenic sites of the previous seasonal A/Brisbane/59/2007 (H1N1) (Bris07) virus remain poorly documented. Here, we produced mAbs against pdm09 and Bris07 HA proteins expressed in human HEK293 cells. Escape mutants were generated using mAbs that exhibited HA inhibition and neutralizing activities. The resulting epitope mapping of the pdm09 HA protein revealed 11 escape mutations including three that were previously described (G172E, N173D and K256E) and eight novel ones (T89R, F128L, G157E, K180E, A212E, R269K, N311T and G478E). Among the six HA mutations that were part of predicted antigenic sites (Ca1, Ca2, Cb, Sa or Sb), three (G172E, N173D and K180E) were within the Sa site. Eight escape mutations (H54N, N55D, N55K, L60H, N203D, A231T, V314I and K464E) were obtained for Bris07 HA, and all but one (N203D, Sb site) were outside the predicted antigenic sites. Our results suggest that the Sa antigenic site is immunodominant in pdm09 HA, whereas the N203D mutation (Sb site), present in three different Bris07 escape mutants, appears as the immunodominant epitope in that strain. The fact that some mutations were not part of predicted antigenic sites reinforces the necessity of further characterizing the HA of additional H1N1 strains.

scholarly journals Contemporary Seasonal Influenza A (H1N1) Virus Infection Primes for a More Robust Response To Split Inactivated Pandemic Influenza A (H1N1) Virus Vaccination in Ferrets

2010 ◽  
Vol 17 (12) ◽  
pp. 1998-2006 ◽  
Author(s):  
Ali H. Ellebedy ◽  
Thomas P. Fabrizio ◽  
Ghazi Kayali ◽  
Thomas H. Oguin ◽  
Scott A. Brown ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Pandemic Influenza ◽  
Influenza A ◽  
Seasonal Influenza ◽  
H1n1 Virus ◽  
H1n1 Influenza ◽  
Influenza Viruses ◽  
Inactivated Vaccine ◽  
H1n1 Influenza Virus ◽  
Influenza A H1n1

ABSTRACT Human influenza pandemics occur when influenza viruses to which the population has little or no immunity emerge and acquire the ability to achieve human-to-human transmission. In April 2009, cases of a novel H1N1 influenza virus in children in the southwestern United States were reported. It was retrospectively shown that these cases represented the spread of this virus from an ongoing outbreak in Mexico. The emergence of the pandemic led to a number of national vaccination programs. Surprisingly, early human clinical trial data have shown that a single dose of nonadjuvanted pandemic influenza A (H1N1) 2009 monovalent inactivated vaccine (pMIV) has led to a seroprotective response in a majority of individuals, despite earlier studies showing a lack of cross-reactivity between seasonal and pandemic H1N1 viruses. Here we show that previous exposure to a contemporary seasonal H1N1 influenza virus and to a lesser degree a seasonal influenza virus trivalent inactivated vaccine is able to prime for a higher antibody response after a subsequent dose of pMIV in ferrets. The more protective response was partially dependent on the presence of CD8+ cells. Two doses of pMIV were also able to induce a detectable antibody response that provided protection from subsequent challenge. These data show that previous infection with seasonal H1N1 influenza viruses likely explains the requirement for only a single dose of pMIV in adults and that vaccination campaigns with the current pandemic influenza vaccines should reduce viral burden and disease severity in humans.

scholarly journals A comparison of live and inactivated influenza A (H1N1) virus vaccines: Short-term immunity

1983 ◽  
Vol 90 (3) ◽  
pp. 351-359 ◽  
Author(s):  
A. Clark ◽  
C. W. Potter ◽  
R. Jennings ◽  
J. P. Nicholl ◽  
A. F. Langrick ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Antibody Response ◽  
Surface Antigen ◽  
Influenza A ◽  
Serum Antibody ◽  
H1n1 Influenza ◽  
Live Attenuated Vaccine ◽  
Challenge Virus ◽  
Influenza A H1n1 ◽  
Aqueous Surface

SUMMARYGroups of volunteers were immunized subcutaneously with one of three inacti vated influenza virus A/USSR/77 (HlNl) vaccine preparations; a whole virus vaccine, a surface-antigen subunit adsorbed vaccine, or an aqueous surface-antigen subunit vaccine. The reactions to immunization were recorded, and the antibody response was measured 1 month later. A fourth group of volunteers were inoculated intranasally with live attentuated A/USSR/77 (H1N1) influenza virus; the reactions and antibody response of these volunteers were also measured. One month after immunization, the incidence of infection by challenge with homologous live attentuated virus was determined for all groups of volunteers. The results showed that all four vaccines used were relatively non-reactogenic, and that inactivated vaccines induced higher titres of serum antibody than the live attenuated vaccine. All the vaccines induced significant protection against challenge virus infection which was directly related to the level of serum HI antibody response.

scholarly journals Epitope Mapping of the Hemagglutinin Molecule of a Highly Pathogenic H5N1 Influenza Virus by Using Monoclonal Antibodies

2007 ◽  
Vol 81 (23) ◽  
pp. 12911-12917 ◽  
Author(s):  
Nikolai V. Kaverin ◽  
Irina A. Rudneva ◽  
Elena A. Govorkova ◽  
Tatyana A. Timofeeva ◽  
Aleksandr A. Shilov ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Amino Acid ◽  
H5n1 Virus ◽  
Antigenic Site ◽  
H5n1 Influenza Virus ◽  
Highly Pathogenic ◽  
H5n1 Influenza ◽  
Antigenic Sites ◽  
Escape Mutants ◽  
Pathogenic H5n1

ABSTRACT We mapped the hemagglutinin (HA) antigenic epitopes of a highly pathogenic H5N1 influenza virus on the three-dimensional HA structure by characterizing escape mutants of a recombinant virus containing A/Vietnam/1203/04 (H5N1) ΔHA and neuraminidase genes in the genetic background of A/Puerto Rico/8/34 (H1N1) virus. The mutants were selected with a panel of eight anti-HA monoclonal antibodies (MAbs), seven to A/Vietnam/1203/04 (H5N1) virus and one to A/Chicken/Pennsylvania/8125/83 (H5N2) virus, and the mutants’ HA genes were sequenced. The amino acid changes suggested three MAb groups: four MAbs reacted with the complex epitope comprising parts of the antigenic site B of H3 HA and site Sa of H1 HA, two MAbs reacted with the epitope corresponding to the antigenic site A in H3 HA, and two MAbs displayed unusual behavior: each recognized amino acid changes at two widely separate antigenic sites. Five changes were detected in amino acid residues not previously reported as changed in H5 escape mutants, and four others had substitutions not previously described. The HA antigenic structure differs substantially between A/Vietnam/1203/04 (H5N1) virus and the low-pathogenic A/Mallard/Pennsylvania/10218/84 (H5N2) virus we previously characterized (N. V. Kaverin et al., J. Gen. Virol. 83:2497-2505, 2002). The hemagglutination inhibition reactions of the MAbs with recent highly pathogenic H5N1 viruses were consistent with the antigenic-site amino acid changes but not with clades and subclades based on H5 phylogenetic analysis. These results provide information on the recognition sites of the MAbs widely used to study H5N1 viruses and demonstrate the involvement of the HA antigenic sites in the evolution of highly pathogenic H5N1 viruses, findings that can be critical for characterizing pathogenesis and vaccine design.

scholarly journals Quantifying the mortality caused by the H1N1 influenza virus during the 2009 pandemic in Mexico

2014 ◽  
Vol 8 (06) ◽  
pp. 742-748 ◽  
Author(s):  
Eusebio Perez-Flores ◽  
Juan Carlos Izquierdo-Puente ◽  
Jose Juan Castillo-Perez ◽  
Gustavo Ramírez-Rosales ◽  
Israel Grijalva-Otero ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Cause Of Death ◽  
Influenza A ◽  
H1n1 Influenza ◽  
The United States ◽  
Study Data ◽  
Death Certificates ◽  
Influenza A H1n1 ◽  
Uniform Probability Distribution ◽  
Source Of Error

Introduction: The frequency and mortality of the pandemic caused by influenza A(H1N1)pdm09 might have been underestimated, especially in developing countries. This study was designed to quantify the possible underestimation of pandemic influenza mortality and evaluate the concordance between the data reported for A(H1N1)pdm09 mortality and the causes of death reported during the pandemic period of April 2009 to February 2010. Methodology: The death certificates of 754 confirmed cases of A(H1N1)pdm09 infection were included in the study. Data was analyzed using the United States Centers for Disease Control and Prevention’s statistical model accounts for the variability in the proportion at each step using the Monte Carlo probabilistic model sampled from a uniform probability distribution. Results: A total of 1,969 deaths were estimated, with an estimated lethality of 5.53 per 100,000 (range, 3.5-8.76 per 100,000) in contrast with the 754 deaths and a lethality of 1.98 per 100,000 infected patients officially reported. In 631 of 754 (83.7%) death certificates from A(H1N1)pdm09 influenza-positive patients, influenza was not mentioned as a cause of death. Conclusions: It is possible that the mortality of the pandemic was three times higher than officially reported in Mexico. One source of error that could explain this underestimation is in the completion of death certificates, because in > 80% of confirmed cases of infection with influenza virus, it was not reported as the cause of death.

scholarly journals The Modified JiuWei QiangHuo Decoction Alleviated Severe Lung Injury Induced by H1N1 Influenza Virus by Regulating the NF-κB Pathway in Mice

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Lijuan Chen ◽  
Xin Yan ◽  
Qianlin Yan ◽  
Jiajun Fan ◽  
Hai Huang ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Lung Injury ◽  
Influenza A ◽  
H1n1 Virus ◽  
Alternative Therapy ◽  
Severe Pneumonia ◽  
H1n1 Influenza ◽  
Influenza A H1n1 ◽  
Lung Injuries ◽  
Severe Lung

A new approach to treat infections of highly pathogenic influenza virus is to inhibit excessive innate immune response. JiuWei QiangHuo decoction has been used for centuries for the treatment of pulmonary disorders in China. In this study, we evaluated the anti-inflammatory activities of the modified JiuWei QiangHuo (MJWQH) decoction in the treatment of influenza A (H1N1) virus-induced severe pneumonia in mice. The results showed that MJWQH significantly increased the survival rate of H1N1-infected mice and suppressed the production of TNF-α, IL-1, IL-6, MCP-1, RANTES, and IFN-αon day 4 after infection. Moreover, oral administration of MJWQH efficiently inhibited virus replication and alleviated the severity of lung injuries. The results also showed that MJWQH may have potential therapeutic effect on severe lung injury induced by H1N1 virus by regulating the NF-κB pathway. Our study suggested that MJWQH might be an alternative therapy for the treatment of viral pneumonia.

scholarly journals Hospitalizations associated with 2009 influenza A (H1N1) and seasonal influenza in Saurashtra region, India

2010 ◽  
Vol 4 (12) ◽  
pp. 834-841 ◽  
Author(s):  
Rajesh K Chudasama ◽  
Umed V Patel ◽  
Pramod B Verma
Keyword(s):  
Influenza Virus ◽  
Median Time ◽  
Influenza A ◽  
Seasonal Influenza ◽  
H1n1 Influenza ◽  
Pandemic H1n1 ◽  
H1n1 Influenza Virus ◽  
Pandemic H1n1 Influenza ◽  
Influenza A H1n1 ◽  
Epidemiological Characteristics

Introduction: This study investigated the clinico-epidemiological characteristics of patients who were hospitalized with 2009 pandemic H1N1 influenza virus infection and seasonal influenza in the Saurashtra region of India. Methodology: From September 2009 to February 2010, a total of 773 patients with influenza virus attending different hospitals in Rajkot city were studied. Real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) testing was used to confirm infection; the clinico-epidemiological features of the disease were closely monitored. Results: Of the 733 patients, 35.4% (274/773) were cases of 2009 pandemic H1N1 influenza and 64.6% (499/773) were cases of seasonal influenza. Of the 274 patients with 2009 pandemic H1N1 influenza, the median age was 29.5 years, and 51.5% were males. Only 1.1% positive patients had recent travel history to an infected region. A median time of five days was observed from onset of illness to influenza A (H1N1) diagnosis, and a median time of six days was reported for hospital stay. All admitted influenza A (H1N1) patients received Oseltamivir drug, but only 16.1% received it within two days of onset of illness. One fourth of the admitted positive patients died. The most common symptoms were cough, fever, sore throat, and shortness of breath. The coexisting conditions were diabetes mellitus, hypertension, chronic pulmonary diseases, and pregnancy (p = 0.001). Chest radiography revealed 93% of the positive patients had pneumonia. Conclusion: The clinical course and outcomes of the 2009 pandemic (H1N1) influenza virus are comparable to those of the currently circulating seasonal influenza, with high mortality in influenza A (H1N1) patients.

scholarly journals mRNA Vaccines Encoding the HA Protein of Influenza A H1N1 Virus Delivered by Cationic Lipid Nanoparticles Induce Protective Immune Responses in Mice

Vaccines ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 123 ◽  
Author(s):  
Xinyu Zhuang ◽  
Yanxin Qi ◽  
Maopeng Wang ◽  
Ning Yu ◽  
Fulong Nan ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Immune Responses ◽  
Influenza A ◽  
Cationic Lipid ◽  
H1n1 Influenza ◽  
Translation Efficiency ◽  
H1n1 Influenza Virus ◽  
Influenza A H1n1 ◽  
Better Than

The design of the mRNA vaccine involves the selection of in vitro transcription (IVT) systems and nonviral delivery vectors. This study aimed to verify the effect of 5’ and 3’ untranslated region (UTR) sequences on the translation efficiency of mRNA. Three modes of IVT-mRNA systems (IVT-mRNA-n1/n2/n3) with diverse UTRs were constructed, and EGFP (enhanced green fluorescent protein) and HA (hemagglutinin) gene of H3N2 influenza virus were introduced into each of them. The results showed that the mode of 5’ and 3’ UTRs originating from human β-globulin was better than the mode of UTRs from human α-globulin, and the n3 mode was the best. mEGFP-n3, mH3HA-n3, and mLuciferease-n3 were prepared to compare the effect of cationic lipid nanoparticle (LNP) with that of mannose-conjugated LNP (LNP-Man) on the efficiency of gene delivery. The results showed that the effect of LNP-Man was better than that of LNP both in vitro and in vivo. Choosing appropriate ligands might help in vaccine design. After selecting the IVT-mRNA-n3 system and delivery vectors, mRNA vaccines were constructed against the H1N1 influenza virus, and C57BL/6 mice were immunized through intranasal administration. The results showed that mRNA vaccines could elicit both humoral and cellular immune responses and completely protect mice from the tenfold LD50 H1N1 influenza virus challenge.

scholarly journals Comparable Disease Severity by Influenza Virus Subtype in the Acute Respiratory Infection Consortium Natural History Study

2020 ◽  
Vol 185 (7-8) ◽  
pp. e1008-e1015
Author(s):  
Christina Schofield ◽  
Rhonda E Colombo ◽  
Stephanie A Richard ◽  
Wei-Ju Chen ◽  
Mary P Fairchok ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Disease Severity ◽  
Department Of Defense ◽  
Symptom Severity ◽  
Influenza A ◽  
H1n1 Influenza ◽  
Influenza B ◽  
Prevention Measures ◽  
Severity Scores ◽  
Influenza A H1n1

Abstract Introduction Since the influenza A/H1N1 pandemic of 2009 to 2010, numerous studies have described the clinical course and outcome of the different subtypes of influenza (A/H1N1, A/H3N2, and B). A recent systematic literature review concluded that there were no appreciable differences in either clinical presentation or disease severity among these subtypes, but study parameters limit the applicability of these results to military populations. We sought to evaluate differences in disease severity among influenza subtypes in a cohort of healthy, primarily outpatient adult U.S. Department of Defense beneficiaries. Materials and Methods From 2009 to 2014, we enrolled otherwise healthy adults age 18 to 65 years with influenza-like illness in an observational cohort study based in 5 U.S. military medical centers. Serial nasopharyngeal swabs were collected for determination of etiology and viral shedding by polymerase chain reaction. The presence and severity of symptoms was assessed by interview and patient diary. Results Over a 5-year period, a total of 157 adults with laboratory-confirmed influenza and influenza subtype were enrolled. Of these, 69 (44%) were positive for influenza A(H1N1), 69 (44%) for influenza A(H3N2), and 19 (12%) for influenza B. About 61% were male, 64% were active duty military personnel, and 72% had received influenza vaccine in the past 8 months. Almost 10% were hospitalized with influenza. Seasonal influenza virus distribution among enrollees mirrored that of nationwide trends each year of study. Individuals with A/H1N1 had upper respiratory composite scores that were lower than those with A/H3N2. Multivariate models indicated that individuals with A(H1N1) and B had increased lower respiratory symptom scores when compared to influenza A(H3N2) (A[H1N1]: 1.51 [95% CI 0.47, 2.55]; B: 1.46 [95% CI 0.09, 2.83]), whereas no other differences in symptom severity scores among influenza A(H1N1), influenza A(H3N2), and influenza B infection were observed. Overall, influenza season (maximum in 2012–2013 season) and female sex of the participant were found to be associated with increased influenza symptom severity. Conclusions Our study of influenza in a cohort of otherwise healthy, outpatient adult Department of Defense beneficiaries over 5 influenza seasons revealed few differences between influenza A(H1N1), influenza A(H3N2), and influenza B infection with respect to self-reported disease severity or clinical outcomes. This study highlights the importance of routine, active, and laboratory-based surveillance to monitor ongoing trends and severity of influenza in various populations to inform prevention measures.

scholarly journals Simultaneous detection and subtyping of H274Y-positive influenza A (H1N1) using pyrosequencing

2011 ◽  
Vol 5 (05) ◽  
pp. 348-352 ◽  
Author(s):  
Wasun Chantratita ◽  
Chonlaphat Sukasem ◽  
Sayomporn Sirinavin ◽  
Nipaporn Sankuntaw ◽  
Chutatip Srichantaratsamee ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
Simultaneous Detection ◽  
Resistance Mutation ◽  
H1n1 Influenza ◽  
Rt Pcr ◽  
H1n1 Influenza Virus ◽  
Oseltamivir Resistance ◽  
Influenza A H1n1 ◽  
H274y Mutation

Introduction: We investigated the frequency of H274Y-positive swine-origin 2009 A (H1N1) influenza virus outbreak in Thailand during May-August 2009.  Methodology: This study sought to find Oseltamivir resistance mutation H274Y by using pyrosequencing. Results: From 8,710 real-time RT-PCR swine-origin 2009 A(H1N1) influenza virus-positive specimens, 100 randomly selected samples identified one such virus with H274Y mutation  using pyrosequencing. Conclusions: The patient probably acquired oseltamivir resistance from natural variation, since he had never received that form of treatment before and recovered from influenza-like symptoms without using anti-influenza drugs.

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