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  1 / 3265 MEDLINE  
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PMID:27997703
Autor:Keam B; Kim MK; Choi Y; Choi SJ; Choe PG; Lee KH; Kim TM; Kim TY; Oh DY; Kim DW; Im SA; Kim NJ; Heo DS; Park WB; Oh MD
Dirección:Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
Título:Optimal timing of influenza vaccination during 3-week cytotoxic chemotherapy cycles.
Fuente:Cancer; 123(5):841-848, 2017 Mar 01.
ISSN:1097-0142
País de publicación:United States
Idioma:eng
Resumen:BACKGROUND: Cytopenia occurs frequently during cytotoxic chemotherapy. Little is known about the optimal timing of influenza vaccination for patients receiving chemotherapy. This study compared the immunogenicity of an influenza vaccine administered concurrently with chemotherapy (day 1) and within the cytopenic period (day 11) during 3-week cytotoxic chemotherapy cycles. METHODS: Adult patients with solid cancer undergoing scheduled 3-week cytotoxic chemotherapy were randomly assigned to receive the 2014-2015 seasonal influenza vaccine on day 1 or 11 during the chemotherapy cycle. Patients were stratified by their age (<60 and ≥60 years) and previous influenza vaccination status. Antibody responses to influenza vaccine strains H1N1, H3N2, and B were measured before and 21 to 28 days after vaccination with a hemagglutination inhibition antibody assay. RESULTS: Ninety-seven patients were randomized into a day 1 group (n = 43) or a day 11 group (n = 54). Eighty-three patients were included in the final analysis. The mean age was 54 (± 11) years. Cancer types included breast (61%) and lung cancer (30%). Baseline characteristics were not significantly different between the groups. Seroprotection rates after vaccination were also not significantly different for the day 1 and 11 groups (strain H1N1, 67% vs 75% [P = .403]; strain H3N2, 77% vs 80% [P = .772]; strain B, 21% vs 27% [P = .472]). Seroconversion rates and postvaccination geometric mean titers were also similar for the groups. Vaccine-related adverse events were more common in the day 11 group (13% vs. 32%; P = .040). CONCLUSIONS: The antibody responses to influenza vaccination on days 1 and 11 during a 3-week cytotoxic chemotherapy cycle were comparable. Influenza vaccination can be performed concurrently with cytotoxic chemotherapy or during the cytopenic period. Cancer 2017;123:841-48. © 2016 American Cancer Society.
Tipo de publicación:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
Nombre de substancia:0 (Influenza Vaccines)


  2 / 3265 MEDLINE  
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PMID:28548881
Autor:Lowen AC
Dirección:Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322; email: anice.lowen@emory.edu.
Título:Constraints, Drivers, and Implications of Influenza A Virus Reassortment.
Fuente:Annu Rev Virol; 4(1):105-121, 2017 Sep 29.
ISSN:2327-0578
País de publicación:United States
Idioma:eng
Resumen:Influenza A viruses are constantly changing. This change accounts for seasonal epidemics, infrequent pandemics, and zoonotic outbreaks. A major mechanism underlying the genetic diversification of influenza A virus is reassortment of intact gene segments between coinfecting viruses. This exchange is possible because of the segmented nature of the viral genome. Here, I first consider the constraints and drivers acting on influenza A virus reassortment, including the likelihood of coinfection at the host and cellular levels, mixing and assembly of heterologous gene segments within coinfected cells, and the fitness associated with reassortant genotypes. I then discuss the implications of reassortment for influenza A virus evolution, including its classically recognized role in the emergence of genetically "shifted" pandemic strains as well as its potential role as a catalyst of genetic drift.
Tipo de publicación:JOURNAL ARTICLE; REVIEW


  3 / 3265 MEDLINE  
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PMID:28768855
Autor:Kamal RP; Blanchfield K; Belser JA; Music N; Tzeng WP; Holiday C; Burroughs A; Sun X; Maines TR; Levine MZ; York IA
Dirección:Battelle Memorial Institute, Atlanta, Georgia, USA KEU7@cdc.gov.
Título:Inactivated H7 Influenza Virus Vaccines Protect Mice despite Inducing Only Low Levels of Neutralizing Antibodies.
Fuente:J Virol; 91(20), 2017 Oct 15.
ISSN:1098-5514
País de publicación:United States
Idioma:eng
Resumen:Avian influenza viruses of the H7 hemagglutinin (HA) subtype present a significant public health threat, as evidenced by the ongoing outbreak of human A(H7N9) infections in China. When evaluated by hemagglutination inhibition (HI) and microneutralization (MN) assays, H7 viruses and vaccines are found to induce lower level of neutralizing antibodies (nAb) than do their seasonal counterparts, making it difficult to develop and evaluate prepandemic vaccines. We have previously shown that purified recombinant H7 HA appear to be poorly immunogenic in that they induce low levels of HI and MN antibodies. In this study, we immunized mice with whole inactivated reverse genetics reassortant (RG) viruses expressing HA and neuraminidase (NA) from 3 different H7 viruses [A/Shanghai/2/2013(H7N9), A/Netherlands/219/2003(H7N7), and A/New York/107/2003(H7N2)] or with human A(H1N1)pdm09 (A/California/07/2009-like) or A(H3N2) (A/Perth16/2009) viruses. Mice produced equivalent titers of antibodies to all viruses as measured by enzyme-linked immunosorbent assay (ELISA). However, the antibody titers induced by H7 viruses were significantly lower when measured by HI and MN assays. Despite inducing very low levels of nAb, H7 vaccines conferred complete protection against homologous virus challenge in mice, and the serum antibodies directed against the HA head region were capable of mediating protection. The apparently low immunogenicity associated with H7 viruses and vaccines may be at least partly related to measuring antibody titers with the traditional HI and MN assays, which may not provide a true measure of protective immunity associated with H7 immunization. This study underscores the need for development of additional correlates of protection for prepandemic vaccines. H7 avian influenza viruses present a serious risk to human health. Preparedness efforts include development of prepandemic vaccines. For seasonal influenza viruses, protection is correlated with antibody titers measured by hemagglutination inhibition (HI) and virus microneutralization (MN) assays. Since H7 vaccines typically induce low titers in HI and MN assays, they have been considered to be poorly immunogenic. We show that in mice H7 whole inactivated virus vaccines (WIVs) were as immunogenic as seasonal WIVs, as they induced similar levels of overall serum antibodies. However, a larger fraction of the antibodies induced by H7 WIV was nonneutralizing Nevertheless, the H7 WIV completely protected mice against homologous viral challenge, and antibodies directed against the HA head were the major contributor toward immune protection. Vaccines against H7 avian influenza viruses may be more effective than HI and virus neutralization assays suggest, and such vaccines may need other methods for evaluation.
Tipo de publicación:JOURNAL ARTICLE
Nombre de substancia:0 (Antibodies, Neutralizing); 0 (Antibodies, Viral); 0 (Hemagglutinin Glycoproteins, Influenza Virus); 0 (Influenza Vaccines); 0 (Vaccines, Inactivated); 0 (hemagglutinin, avian influenza A virus); EC 3.2.1.18 (Neuraminidase)


  4 / 3265 MEDLINE  
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PMID:28877235
Autor:Monamele GC; Vernet MA; Njankouo MR; Victoir K; Akoachere JF; Anong D; Njouom R
Dirección:National Influenza Centre, Centre Pasteur du Cameroun, Yaoundé, Cameroon.
Título:Genetic and antigenic characterization of influenza A(H3N2) in Cameroon during the 2014-2016 influenza seasons.
Fuente:PLoS One; 12(9):e0184411, 2017.
ISSN:1932-6203
País de publicación:United States
Idioma:eng
Resumen:The first outbreak of influenza A(H3N2) occurred in 1968 and caused the third flu pandemic of the 20th century. It has affected multiple countries over time. The best strategy to reduce the burden of influenza is through vaccination whose efficacy varies with respect to the circulating strains. This study was performed to better understand the molecular evolution of influenza A(H3N2) and assess vaccine efficacy in Cameroon. Complete sequences of three gene segments were obtained from 2014 to 2016 influenza seasons in Cameroon. Hemagglutinin (HA), Neuraminidase (NA) and matrix (M) genes of 35 A(H3N2) virus strains were amplified and sequenced. Predicted vaccine efficacy was measured using the Pepitope model. Phylogenetic analysis of the HA gene showed that all Cameroonian strains had evolved away from the 3C.1-A/Texas/50/2012-like clade. Globally, 2014 virus strains clustered with the 2015-2016 vaccine strain, 3C.3a-A/Switzerland/9715293/2013, whereas 2015 and 2016 virus strains clustered with the 2016-2017 vaccine strain, 3C.2a-A/HongKong/4801/2014. In order to determine the genotypic drug susceptibility to neuraminidase inhibitors and amantadine, the NA and M2 protein coding sequences were analyzed. There was no strain with characteristic mutation for resistance to neuraminidase inhibitors, per contra; all strains possessed the substitution S31N, peculiar of resistance to adamantanes. There was drift in influenza A(H3N2) dominant epitopes B (2014 and 2015) to epitopes A (2016) with a theoretical efficiency in vaccine ranging from low to moderate. The presence of several antigenic site mutations among H3N2 virus strains between 2014-2016 influenza seasons in Cameroon confirms the progressing evolution of circulating H3N2 strains.
Tipo de publicación:JOURNAL ARTICLE
Nombre de substancia:0 (Epitopes); 0 (Hemagglutinin Glycoproteins, Influenza Virus); 0 (Influenza Vaccines); 0 (RNA, Viral)


  5 / 3265 MEDLINE  
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PMID:28034300
Autor:Maljkovic Berry I; Melendrez MC; Li T; Hawksworth AW; Brice GT; Blair PJ; Halsey ES; Williams M; Fernandez S; Yoon IK; Edwards LD; Kuschner R; Lin X; Thomas SJ; Jarman RG
Dirección:Walter Reed Army Institute of Research, Silver Spring, MD, USA. irina.maljkovicberry.ctr@mail.mil.
Título:Frequency of influenza H3N2 intra-subtype reassortment: attributes and implications of reassortant spread.
Fuente:BMC Biol; 14(1):117, 2016 Dec 29.
ISSN:1741-7007
País de publicación:England
Idioma:eng
Resumen:BACKGROUND: Increasing evidence suggests that influenza reassortment not only contributes to the emergence of new human pandemics but also plays an important role in seasonal influenza epidemics, disease severity, evolution, and vaccine efficacy. We studied this process within 2091 H3N2 full genomes utilizing a combination of the latest reassortment detection tools and more conventional phylogenetic analyses. RESULTS: We found that the amount of H3N2 intra-subtype reassortment depended on the number of sampled genomes, occurred with a steady frequency of 3.35%, and was not affected by the geographical origins, evolutionary patterns, or previous reassortment history of the virus. We identified both single reassortant genomes and reassortant clades, each clade representing one reassortment event followed by successful spread of the reassorted variant in the human population. It was this spread that was mainly responsible for the observed high presence of H3N2 intra-subtype reassortant genomes. The successfully spread variants were generally sampled within one year of their formation, highlighting the risk of their rapid spread but also presenting an opportunity for their rapid detection. Simultaneous spread of several different reassortant lineages was observed, and despite their limited average lifetime, second and third generation reassortment was detected, as well as reassortment between viruses belonging to different vaccine-associated clades, likely displaying differing antigenic properties. Some of the spreading reassortants remained confined to certain geographical regions, while others, sharing common properties in amino acid positions of the HA, NA, and PB2 segments, were found throughout the world. CONCLUSIONS: Detailed surveillance of seasonal influenza reassortment patterns and variant properties may provide unique information needed for prediction of spread and construction of future influenza vaccines.
Tipo de publicación:JOURNAL ARTICLE


  6 / 3265 MEDLINE  
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PMID:28510127
Autor:Zhirnov OP; Akulich KA; Lipatova AV; Usachev EV
Dirección:Ivanovsky Research Institute of Virology, Russian Academy of Medical Sciences, Moscow, 123098, Russia. zhirnov@inbox.ru.
Título:Negative-sense virion RNA of segment 8 (NS) of influenza a virus is able to translate in vitro a new viral protein.
Fuente:Dokl Biochem Biophys; 473(1):122-127, 2017 Mar.
ISSN:1608-3091
País de publicación:Russia (Federation)
Idioma:eng
Resumen:It was shown that full-length virion RNA of segment 8 of influenza virus A/Aichi/2/68 (H3N2) can initiate the synthesis of two major polypeptides with molecular weights of 23 and 13 kD and a minor polypeptide with a molecular weight of 19 kDa, which specifically reacted with the antibodies to the 30-membered peptide of the central part of the NSP protein of influenza A virus. Thus, the genomic-polarity RNA of segment 8 of influenza virus A has a translational template function. These data provide further confirmation of the concept of the bipolar (ambisens) strategy of functioning of the influenza A virus genome.
Tipo de publicación:JOURNAL ARTICLE
Nombre de substancia:0 (RNA, Viral); 0 (Viral Proteins)


  7 / 3265 MEDLINE  
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PMID:28740382
Autor:Wang C; Zhu W; Wang BZ
Dirección:Center for Inflammation, Immunity and Infection, Georgia State University Institute for Biomedical Sciences, Atlanta, GA, USA.
Título:Dual-linker gold nanoparticles as adjuvanting carriers for multivalent display of recombinant influenza hemagglutinin trimers and flagellin improve the immunological responses in vivo and in vitro.
Fuente:Int J Nanomedicine; 12:4747-4762, 2017.
ISSN:1178-2013
País de publicación:New Zealand
Idioma:eng
Resumen:Vaccination is the most cost-effective means of infectious disease control. Although current influenza vaccines are effective in battling closely matched strains, such vaccines have major limitations such as the requirement to produce new vaccines every season, an egg-dependent production system, long production periods, uncertainty in matching the vaccine to circulating strains, and the inability to react to new influenza pandemics resulting from genetic drift or shift. To overcome the intrinsic limitations of the conventional influenza vaccine, we have designed dual-linker gold nanoparticles (AuNPs) conjugated with both recombinant trimetric A/Aichi/2/68 (H3N2), hemagglutinin (HA) and TLR5 agonist flagellin (FliC) as a novel vaccine approach. Click chemistry and metal-chelating reactions were used to couple the two proteins. The conjugated proteins were found to possess high coupling specificity, high stability in harsh environments, high conjugation efficiency, and the ability to keep the appropriate protein conformations for immunogenicity and immunostimulation. Both AuNPs-HA/FliC and AuNPs-HA formulations induced higher levels of antibody responses than a mixture of soluble HA and FliC proteins when administered via a single intranasal immunization in mice. To further investigate the adjuvancy of these nanoparticles, in vitro experiments were conducted in both the JAWS II dendritic cell (DC) line and bone marrow-derived DC (BMDC) models. The results showed that dual-conjugated AuNPs were rapidly targeted and taken up by DCs. Consequently, DCs were induced toward maturation, as demonstrated by high levels of cytokine secretions and membrane costimulatory molecule expression. T cell proliferation was observed when splenic T cells were cocultured with AuNPs-HA/FliC-primed BMDCs. These results suggest that dual-conjugated AuNPs are effective at simultaneously displaying antigens and adjuvants in an oriented, multivalent format and can promote a strong immune response by activating DCs and T cells.
Tipo de publicación:JOURNAL ARTICLE
Nombre de substancia:0 (Adjuvants, Immunologic); 0 (Drug Carriers); 0 (Hemagglutinin Glycoproteins, Influenza Virus); 0 (Influenza Vaccines); 12777-81-0 (Flagellin); 7440-57-5 (Gold)


  8 / 3265 MEDLINE  
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PMID:28870977
Autor:; COMMITTEE ON INFECTIOUS DISEASES
Título:Recommendations for Prevention and Control of Influenza in Children, 2017 - 2018.
Fuente:Pediatrics; 140(4), 2017 Oct.
ISSN:1098-4275
País de publicación:United States
Idioma:eng
Resumen:This statement updates the recommendations for routine use of the seasonal influenza vaccine and antiviral medications for the prevention and treatment of influenza in children. The American Academy of Pediatrics recommends annual seasonal influenza immunization for everyone 6 months and older, including children and adolescents. Highlights for the upcoming 2017-2018 season include the following:1. Annual universal influenza immunization is indicated with either a trivalent or quadrivalent (no preference) inactivated vaccine;2. The 2017-2018 influenza A (H1N1) vaccine strain differs from that contained in the 2016-2017 seasonal vaccines. The 2017-2018 influenza A (H3N2) vaccine strain and influenza B vaccine strains included in the trivalent and quadrivalent vaccines are the same as those contained in the 2016-2017 seasonal vaccines: a. trivalent vaccine contains an A/Michigan/45/2015 (H1N1)pdm09-like virus, an A/Hong Kong/4801/2014 (H3N2)-like virus, and a B/Brisbane/60/2008-like virus (B/Victoria lineage); and b. quadrivalent vaccine contains an additional B virus (B/Phuket/3073/2013-like virus [B/Yamagata lineage]);3. Quadrivalent live attenuated influenza vaccine (LAIV4) is not recommended for use in any setting in the United States during the 2017-2018 influenza season. This interim recommendation, originally made in 2016, followed observational data from the US Influenza Vaccine Effectiveness Network revealing that LAIV4 performed poorly against influenza A (H1N1)pdm09 viruses in recent influenza seasons;4. All children with an egg allergy of any severity can receive an influenza vaccine without any additional precautions beyond those recommended for any vaccine;5. All health care personnel should receive an annual seasonal influenza vaccine, a crucial step in preventing influenza and reducing health care-associated influenza infections, because health care personnel often care for individuals at high risk for influenza-related complications; and6. Pediatricians should attempt to promptly identify children suspected of having influenza infection for timely initiation of antiviral treatment, when indicated, to reduce morbidity and mortality. Best results are seen when treated within 48 hours of symptom onset.
Tipo de publicación:JOURNAL ARTICLE; PRACTICE GUIDELINE
Nombre de substancia:0 (Antiviral Agents); 0 (Influenza Vaccines)


  9 / 3265 MEDLINE  
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PMID:28117657
Autor:Chen H; Zhou X; Zheng J; Kwoh CK
Dirección:School of Computer Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue, 639798, Singapore, Singapore.
Título:Rules of co-occurring mutations characterize the antigenic evolution of human influenza A/H3N2, A/H1N1 and B viruses.
Fuente:BMC Med Genomics; 9(Suppl 3):69, 2016 Dec 05.
ISSN:1755-8794
País de publicación:England
Idioma:eng
Resumen:BACKGROUND: The human influenza viruses undergo rapid evolution (especially in hemagglutinin (HA), a glycoprotein on the surface of the virus), which enables the virus population to constantly evade the human immune system. Therefore, the vaccine has to be updated every year to stay effective. There is a need to characterize the evolution of influenza viruses for better selection of vaccine candidates and the prediction of pandemic strains. Studies have shown that the influenza hemagglutinin evolution is driven by the simultaneous mutations at antigenic sites. Here, we analyze simultaneous or co-occurring mutations in the HA protein of human influenza A/H3N2, A/H1N1 and B viruses to predict potential mutations, characterizing the antigenic evolution. METHODS: We obtain the rules of mutation co-occurrence using association rule mining after extracting HA1 sequences and detect co-mutation sites under strong selective pressure. Then we predict the potential drifts with specific mutations of the viruses based on the rules and compare the results with the "observed" mutations in different years. RESULTS: The sites under frequent mutations are in antigenic regions (epitopes) or receptor binding sites. CONCLUSIONS: Our study demonstrates the co-occurring site mutations obtained by rule mining can capture the evolution of influenza viruses, and confirms that cooperative interactions among sites of HA1 protein drive the influenza antigenic evolution.
Tipo de publicación:JOURNAL ARTICLE
Nombre de substancia:0 (Hemagglutinin Glycoproteins, Influenza Virus); 0 (Hepatitis Antigens)


  10 / 3265 MEDLINE  
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PMID:28981486
Autor:Blanton L; Wentworth DE; Alabi N; Azziz-Baumgartner E; Barnes J; Brammer L; Burns E; Davis CT; Dugan VG; Fry AM; Garten R; Grohskopf LA; Gubareva L; Kniss K; Lindstrom S; Mustaquim D; Olsen SJ; Roguski K; Taylor C; Trock S; Xu X; Katz J; Jernigan D
Dirección:Influenza Division, National Center for Immunization and Respiratory Diseases, CDC.
Título:Update: Influenza Activity - United States and Worldwide, May 21-September 23, 2017.
Fuente:MMWR Morb Mortal Wkly Rep; 66(39):1043-1051, 2017 Oct 06.
ISSN:1545-861X
País de publicación:United States
Idioma:eng
Resumen:During May 21-September 23, 2017,* the United States experienced low-level seasonal influenza virus activity; however, beginning in early September, CDC received reports of a small number of localized influenza outbreaks caused by influenza A(H3N2) viruses. In addition to influenza A(H3N2) viruses, influenza A(H1N1)pdm09 and influenza B viruses were detected during May-September worldwide and in the United States. Influenza B viruses predominated in the United States from late May through late June, and influenza A viruses predominated beginning in early July. The majority of the influenza viruses collected and received from the United States and other countries during that time have been characterized genetically or antigenically as being similar to the 2017 Southern Hemisphere and 2017-18 Northern Hemisphere cell-grown vaccine reference viruses; however, a smaller proportion of the circulating A(H3N2) viruses showed similarity to the egg-grown A(H3N2) vaccine reference virus which represents the A(H3N2) viruses used for the majority of vaccine production in the United States. Also, during May 21-September 23, 2017, CDC confirmed a total of 33 influenza variant virus infections; two were influenza A(H1N2) variant (H1N2v) viruses (Ohio) and 31 were influenza A(H3N2) variant (H3N2v) viruses (Delaware [1], Maryland [13], North Dakota [1], Pennsylvania [1], and Ohio [15]). An additional 18 specimens from Maryland have tested presumptive positive for H3v and further analysis is being conducted at CDC.
Tipo de publicación:JOURNAL ARTICLE



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