scholarly journals ANALYSIS OF POPULATION IMMUNITY AGAINST INFLUENZA PRIOR TO 2014 AND 2015 EPIDEMIC SEASONS

2017 ◽  
pp. 53-60 ◽  
Author(s):  
A. V. Shipovalov ◽  
A. G. Durymanov ◽  
O. V. Petrova ◽  
E. V. Ivanova ◽  
A. V. Epanchintseva ◽  
...  
Keyword(s):  
Human Blood ◽  
Influenza A ◽  
Seasonal Influenza ◽  
Vaccination Campaign ◽  
Herd Immunity ◽  
Influenza Viruses ◽  
The Urals ◽  
Population Immunity ◽  
Clade 2.3.2.1C ◽  
Sera Samples

Aim. Control for the population herd immunity against seasonal influenza viruses as well as for emergence of antibodies against influenza with pandemic potential in human blood sera. Materials and methods. HAI reaction against vaccine and epidemic influenza viruses as well as HPAI viruses A/rook/Chany/32/2015 (H5N1) (clade 2.3.2.1c.) andA/Anhui/01/2013 (H7N9). Results. Among all the sera samples collected in the autumn of 2014 and 2015, none had reacted in HAI against A(H5N1) and A(H7N9) antigens even at 1:10 dilution. Among samples collected in autumn 2014, 41% were positive to A/Califorrna/07/09(HlNlpdm09) virus, 36% - A/Texas/50/2012 (H3N2), 40% - B/Brisbane/60/2008 (Vict.lin.) and 47% reacted in HAI against the B/Massachusetts/2/2012 (Yam.lin.) strain. 22% of all the samples had a titer of at least 40 against all the antigens and only 10% in HAI had a titer of 40 or more against all the vaccine strains. Among the samples collected in autumn 2015, the number of seropositive against A/Califorrna/07/09(HlNlpdm09) varied from 31% in the Urals FD to 46% in the Southern FD. The amount of seropositive against A/Switzerland/9715293/13 (H3N2) strain was at the level of 4 - 13% in all the FDs except Urals, where this parameter was slightly above 30%. The amount of seropositive against vaccine influenza В viruses varied from 23 to 76%. Only 2% of sera had titers in HAI of 40 or above against all the vaccine strains, 29% of all the samples were seronegative. Conclusion. Population immunity in Russia against influenza A(H3N2) is at a very low level, thus socially significant consequences of influenza epidemics in many aspects will depend on the vaccination campaign of autumn 2016.

scholarly journals Severe cases of seasonal influenza in Russia in 2017-2018

2019 ◽  
pp. 58-64 ◽  
Author(s):  
S. V. Svyatchenko ◽  
A. G. Durymanov ◽  
N. P. Kolosova ◽  
A. S. Gudymo ◽  
N. I. Goncharova ◽  
...  
Keyword(s):  
Influenza A ◽  
Seasonal Influenza ◽  
Effective Means ◽  
Herd Immunity ◽  
Clinical Signs ◽  
Neuraminidase Inhibitor ◽  
Influenza Viruses ◽  
Epidemic Season ◽  
Antibody Titers

Aim.Evaluation of herd immunity prior to the 2017-2018 influenza season, and characterization of influenza viruses isolated from severe or fatal influenza cases and from influenza cases in people vaccinated in the fall of 2017.Materials and methods.Evaluation of herd immunity in hemagglutination inhibition assay. Isolation of influenza viruses. Antigenic and genetic analysis.Results.Prior to epidemic season 33-47% of blood sera samples collected on the territory of Russia showed presence of protective antibody titers against vaccine strains of influenza A, 24-30% of samples — against B/Victoria. During 2017-2018 epidemic season 87 influenza A and B viruses were isolated. A(H1N1)pdm09 strains belonged to clade 6B.1, B/Yamagata strains to clade 3, and B/Victoria strains to clade 1A; they were antigenically similar to corresponding vaccine strains. A(H3N2) viruses belonged to clade 3C.2a and were difficult to characterize antigenically. One strain of influenza virus А(H1N1pdm09) was resistant to oseltamivir and had H275Y amino acid substitution in neuraminidase. All other isolates were susceptible to neuraminidase inhibitors.Conclusion.Influenza vaccination with vaccine effective against current circulating strains and treatment with neuraminidase inhibitor drugs at first manifestation of clinical signs of influenza disease are effective means of population protection against influenza.

scholarly journals Next generation methodology for updating HA vaccines against emerging human seasonal influenza A(H3N2) viruses

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
James D. Allen ◽  
Ted M. Ross
Keyword(s):  
Influenza Virus ◽  
Immune Responses ◽  
Influenza A ◽  
Seasonal Influenza ◽  
Influenza Viruses ◽  
Next Generation ◽  
Virus Infections ◽  
Wild Type ◽  
Influenza Hemagglutinin ◽  
H3n2 Influenza

AbstractWhile vaccines remain the best tool for preventing influenza virus infections, they have demonstrated low to moderate effectiveness in recent years. Seasonal influenza vaccines typically consist of wild-type influenza A and B viruses that are limited in their ability to elicit protective immune responses against co-circulating influenza virus variant strains. Improved influenza virus vaccines need to elicit protective immune responses against multiple influenza virus drift variants within each season. Broadly reactive vaccine candidates potentially provide a solution to this problem, but their efficacy may begin to wane as influenza viruses naturally mutate through processes that mediates drift. Thus, it is necessary to develop a method that commercial vaccine manufacturers can use to update broadly reactive vaccine antigens to better protect against future and currently circulating viral variants. Building upon the COBRA technology, nine next-generation H3N2 influenza hemagglutinin (HA) vaccines were designed using a next generation algorithm and design methodology. These next-generation broadly reactive COBRA H3 HA vaccines were superior to wild-type HA vaccines at eliciting antibodies with high HAI activity against a panel of historical and co-circulating H3N2 influenza viruses isolated over the last 15 years, as well as the ability to neutralize future emerging H3N2 isolates.

scholarly journals Molecular Characterization of Seasonal Influenza A and B from Hospitalized Patients in Thailand in 2018–2019

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 977
Author(s):  
Kobporn Boonnak ◽  
Chayasin Mansanguan ◽  
Dennis Schuerch ◽  
Usa Boonyuen ◽  
Hatairat Lerdsamran ◽  
...  
Keyword(s):  
Amino Acid ◽  
Influenza A ◽  
Seasonal Influenza ◽  
Influenza Viruses ◽  
Surface Proteins ◽  
Antigenic Drift ◽  
Influenza B ◽  
Receptor Binding Site ◽  
Antigenic Sites ◽  
Ha Protein

Influenza viruses continue to be a major public health threat due to the possible emergence of more virulent influenza virus strains resulting from dynamic changes in virus adaptability, consequent of functional mutations and antigenic drift in surface proteins, especially hemagglutinin (HA) and neuraminidase (NA). In this study, we describe the genetic and evolutionary characteristics of H1N1, H3N2, and influenza B strains detected in severe cases of seasonal influenza in Thailand from 2018 to 2019. We genetically characterized seven A/H1N1 isolates, seven A/H3N2 isolates, and six influenza B isolates. Five of the seven A/H1N1 viruses were found to belong to clade 6B.1 and were antigenically similar to A/Switzerland/3330/2017 (H1N1), whereas two isolates belonged to clade 6B.1A1 and clustered with A/Brisbane/02/2018 (H1N1). Interestingly, we observed additional mutations at antigenic sites (S91R, S181T, T202I) as well as a unique mutation at a receptor binding site (S200P). Three-dimensional (3D) protein structure analysis of hemagglutinin protein reveals that this unique mutation may lead to the altered binding of the HA protein to a sialic acid receptor. A/H3N2 isolates were found to belong to clade 3C.2a2 and 3C.2a1b, clustering with A/Switzerland/8060/2017 (H3N2) and A/South Australia/34/2019 (H3N2), respectively. Amino acid sequence analysis revealed 10 mutations at antigenic sites including T144A/I, T151K, Q213R, S214P, T176K, D69N, Q277R, N137K, N187K, and E78K/G. All influenza B isolates in this study belong to the Victoria lineage. Five out of six isolates belong to clade 1A3-DEL, which relate closely to B/Washington/02/2009, with one isolate lacking the three amino acid deletion on the HA segment at position K162, N163, and D164. In comparison to the B/Colorado/06/2017, which is the representative of influenza B Victoria lineage vaccine strain, these substitutions include G129D, G133R, K136E, and V180R for HA protein. Importantly, the susceptibility to oseltamivir of influenza B isolates, but not A/H1N1 and A/H3N2 isolates, were reduced as assessed by the phenotypic assay. This study demonstrates the importance of monitoring genetic variation in influenza viruses regarding how acquired mutations could be associated with an improved adaptability for efficient transmission.

scholarly journals Dynamic interactions of influenza viruses in Hong Kong during 1998-2018

2019 ◽  
Author(s):  
Wan Yang ◽  
Eric H. Y. Lau ◽  
Benjamin J. Cowling
Keyword(s):  
Hong Kong ◽  
Influenza A ◽  
Vaccine Development ◽  
Immune Escape ◽  
Influenza Viruses ◽  
Influenza Surveillance ◽  
Influenza Epidemic ◽  
Inference System ◽  
Population Immunity ◽  
Cross Immunity

AbstractInfluenza epidemics cause substantial morbidity and mortality every year worldwide. Currently, two influenza A subtypes, A(H1N1) and A(H3N2), and type B viruses co-circulate in humans and infection with one type/subtype could provide cross-protection against the others. However, it remains unclear how such ecologic competition via cross-immunity and antigenic mutations that allow immune escape impact influenza epidemic dynamics at the population level. Here we develop a comprehensive model-inference system and apply it to study the evolutionary and epidemiological dynamics of the three influenza types/subtypes in Hong Kong, a city of global public health significance for influenza epidemic and pandemic control. Utilizing long-term influenza surveillance data since 1998, we are able to estimate the strength of cross-immunity between each virus-pairs, the timing and frequency of punctuated changes in population immunity in response to antigenic mutations in influenza viruses, and key epidemiological parameters over the last 20 years including the 2009 pandemic. We find evidence of cross-immunity in all types/subtypes, with strongest cross-immunity from A(H1N1) against A(H3N2). Our results also suggest that A(H3N2) may undergo antigenic mutations in both summers and winters and thus monitoring the virus in both seasons may be important for vaccine development. Overall, our study reveals intricate epidemiological interactions and underscores the importance of simultaneous monitoring of population immunity, incidence rates, and viral genetic and antigenic changes.

scholarly journals Broadly Reactive H2 Hemagglutinin Vaccines Elicit Cross-Reactive Antibodies in Ferrets Preimmune to Seasonal Influenza A Viruses

mSphere ◽  
2021 ◽  
Vol 6 (2) ◽  
Author(s):  
Z. Beau Reneer ◽  
Amanda L. Skarlupka ◽  
Parker J. Jamieson ◽  
Ted M. Ross
Keyword(s):  
Influenza Virus ◽  
Immune Responses ◽  
Recombinant Proteins ◽  
Human Population ◽  
Influenza A ◽  
Seasonal Influenza ◽  
Influenza Viruses ◽  
Wild Type ◽  
Influenza A Viruses ◽  
Global Pandemic

ABSTRACT Influenza vaccines have traditionally been tested in naive mice and ferrets. However, humans are first exposed to influenza viruses within the first few years of their lives. Therefore, there is a pressing need to test influenza virus vaccines in animal models that have been previously exposed to influenza viruses before being vaccinated. In this study, previously described H2 computationally optimized broadly reactive antigen (COBRA) hemagglutinin (HA) vaccines (Z1 and Z5) were tested in influenza virus “preimmune” ferret models. Ferrets were infected with historical, seasonal influenza viruses to establish preimmunity. These preimmune ferrets were then vaccinated with either COBRA H2 HA recombinant proteins or wild-type H2 HA recombinant proteins in a prime-boost regimen. A set of naive preimmune or nonpreimmune ferrets were also vaccinated to control for the effects of the multiple different preimmunities. All of the ferrets were then challenged with a swine H2N3 influenza virus. Ferrets with preexisting immune responses influenced recombinant H2 HA-elicited antibodies following vaccination, as measured by hemagglutination inhibition (HAI) and classical neutralization assays. Having both H3N2 and H1N1 immunological memory regardless of the order of exposure significantly decreased viral nasal wash titers and completely protected all ferrets from both morbidity and mortality, including the mock-vaccinated ferrets in the group. While the vast majority of the preimmune ferrets were protected from both morbidity and mortality across all of the different preimmunities, the Z1 COBRA HA-vaccinated ferrets had significantly higher antibody titers and recognized the highest number of H2 influenza viruses in a classical neutralization assay compared to the other H2 HA vaccines. IMPORTANCE H1N1 and H3N2 influenza viruses have cocirculated in the human population since 1977. Nearly every human alive today has antibodies and memory B and T cells against these two subtypes of influenza viruses. H2N2 influenza viruses caused the 1957 global pandemic and people born after 1968 have never been exposed to H2 influenza viruses. It is quite likely that a future H2 influenza virus could transmit within the human population and start a new global pandemic, since the majority of people alive today are immunologically naive to viruses of this subtype. Therefore, an effective vaccine for H2 influenza viruses should be tested in an animal model with previous exposure to influenza viruses that have circulated in humans. Ferrets were infected with historical influenza A viruses to more accurately mimic the immune responses in people who have preexisting immune responses to seasonal influenza viruses. In this study, preimmune ferrets were vaccinated with wild-type (WT) and COBRA H2 recombinant HA proteins in order to examine the effects that preexisting immunity to seasonal human influenza viruses have on the elicitation of broadly cross-reactive antibodies from heterologous vaccination.

scholarly journals In Vitro Antiviral Activity of Favipiravir (T-705) against Drug-Resistant Influenza and 2009 A(H1N1) Viruses

2010 ◽  
Vol 54 (6) ◽  
pp. 2517-2524 ◽  
Author(s):  
Katrina Sleeman ◽  
Vasiliy P. Mishin ◽  
Varough M. Deyde ◽  
Yousuke Furuta ◽  
Alexander I. Klimov ◽  
...  
Keyword(s):  
Influenza A ◽  
Seasonal Influenza ◽  
Mdck Cells ◽  
Antiviral Effect ◽  
Plaque Formation ◽  
Influenza Viruses ◽  
New Drugs ◽  
Yield Reduction ◽  
Wide Range

ABSTRACT Favipiravir (T-705) has previously been shown to have a potent antiviral effect against influenza virus and some other RNA viruses in both cell culture and in animal models. Currently, favipiravir is undergoing clinical evaluation for the treatment of influenza A and B virus infections. In this study, favipiravir was evaluated in vitro for its ability to inhibit the replication of a representative panel of seasonal influenza viruses, the 2009 A(H1N1) strains, and animal viruses with pandemic (pdm) potential (swine triple reassortants, H2N2, H4N2, avian H7N2, and avian H5N1), including viruses which are resistant to the currently licensed anti-influenza drugs. All viruses were tested in a plaque reduction assay with MDCK cells, and a subset was also tested in both yield reduction and focus inhibition (FI) assays. For the majority of viruses tested, favipiravir significantly inhibited plaque formation at 3.2 μM (0.5 μg/ml) (50% effective concentrations [EC50s] of 0.19 to 22.48 μM and 0.03 to 3.53 μg/ml), and for all viruses, with the exception of a single dually resistant 2009 A(H1N1) virus, complete inhibition of plaque formation was seen at 3.2 μM (0.5 μg/ml). Due to the 2009 pandemic and increased drug resistance in circulating seasonal influenza viruses, there is an urgent need for new drugs which target influenza. This study demonstrates that favipiravir inhibits in vitro replication of a wide range of influenza viruses, including those resistant to currently available drugs.

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 Phase III Randomized, Double-Blind Study Comparing Single-Dose Intravenous Peramivir with Oral Oseltamivir in Patients with Seasonal Influenza Virus Infection

2011 ◽  
Vol 55 (11) ◽  
pp. 5267-5276 ◽  
Author(s):  
Shigeru Kohno ◽  
Muh-Yong Yen ◽  
Hee-Jin Cheong ◽  
Nobuo Hirotsu ◽  
Tadashi Ishida ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Influenza A ◽  
Seasonal Influenza ◽  
Influenza Virus Infection ◽  
Influenza Viruses ◽  
Phase Iii ◽  
Controlled Study ◽  
Double Blind Study ◽  
Double Blind

ABSTRACTAntiviral medications with activity against influenza viruses are important in controlling influenza. We compared intravenous peramivir, a potent neuraminidase inhibitor, with oseltamivir in patients with seasonal influenza virus infection. In a multinational, multicenter, double-blind, double-dummy randomized controlled study, patients aged ≥20 years with influenza A or B virus infection were randomly assigned to receive either a single intravenous infusion of peramivir (300 or 600 mg) or oral administration of oseltamivir (75 mg twice a day [b.i.d.] for 5 days). To demonstrate the noninferiority of peramivir in reducing the time to alleviation of influenza symptoms with hazard model analysis and a noninferiority margin of 0.170, we planned to recruit 1,050 patients in South Korea, Japan, and Taiwan. A total of 1,091 patients (364 receiving 300 mg and 362 receiving 600 mg of peramivir; 365 receiving oseltamivir) were included in the intent-to-treat infected population. The median durations of influenza symptoms were 78.0, 81.0, and 81.8 h in the groups treated with 300 mg of peramivir, 600 mg of peramivir, and oseltamivir, respectively. The hazard ratios of the 300- and 600-mg-peramivir groups compared to the oseltamivir group were 0.946 (97.5% confidence interval [CI], 0.793, 1.129) and 0.970 (97.5% CI, 0.814, 1.157), respectively. Both peramivir groups were noninferior to the oseltamivir group (97.5% CI, <1.170). The overall incidence of adverse drug reactions was significantly lower in the 300-mg-peramivir group, but the incidence of severe reactions in either peramivir group was not different from that in the oseltamivir group. Thus, a single intravenous dose of peramivir may be an alternative to a 5-day oral dose of oseltamivir for patients with seasonal influenza virus infection.

scholarly journals H3N2 Virus as Causative Agent of ARDS Requiring Extracorporeal Membrane Oxygenation Support

2014 ◽  
Vol 2014 ◽  
pp. 1-3
Author(s):  
Adriano Peris ◽  
Giovanni Zagli ◽  
Pasquale Bernardo ◽  
Massimo Bonacchi ◽  
Morena Cozzolino ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Extracorporeal Membrane Oxygenation ◽  
Influenza A ◽  
Seasonal Influenza ◽  
Influenza Season ◽  
Influenza Viruses ◽  
H3n2 Virus ◽  
Membrane Oxygenation ◽  
Viral Aetiology ◽  
Increased Risk

Pandemic influenza virus A(H1N1) 2009 was associated with a higher risk of viral pneumonia in comparison with seasonal influenza viruses. The influenza season 2011-2012 was characterized by the prevalent circulation of influenza A(H3N2) viruses. Whereas most H3N2 patients experienced mild, self-limited influenza-like illness, some patients were at increased risk for influenza complications because of age or underlying medical conditions. Cases presented were patients admitted to the Intensive Care Unit (ICU) of ECMO referral center (Careggi Teaching Hospital, Florence, Italy). Despite extracorporeal membrane oxygenation treatment (ECMO), one patient with H3N2-induced ARDS did not survive. Our experience suggests that viral aetiology is becoming more important and hospitals should be able to perform a fast differential diagnosis between bacterial and viral aetiology.

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