scholarly journals ANTIBODY RESPONSE OF HUMAN BEINGS FOLLOWING VACCINATION WITH INFLUENZA VIRUSES

1942 ◽  
Vol 75 (5) ◽  
pp. 495-511 ◽  
Author(s):  
G. K. Hirst ◽  
E. R. Rickard ◽  
Loring Whitman ◽  
F. L. Horsfall
Keyword(s):  
Influenza Virus ◽  
Antibody Response ◽  
Influenza A ◽  
Geometric Mean ◽  
Allantoic Fluid ◽  
Influenza Viruses ◽  
Human Beings ◽  
Significant Difference ◽  
Antibody Levels

Eleven different preparations of influenza virus were used to vaccinate large groups of human beings. The antibody response to these vaccines was measured by means of the in vitro agglutination inhibition test, and the geometric mean titers of sera taken 2 weeks after vaccination were compared. From these comparisons the following conclusions were drawn: 1. There was a wide individual variation in the antibody response of human beings to the same preparation of influenza virus administrated subcutaneously. The amount of antibody produced by a group with a low prevaccination antibody level was very nearly the same as the amount produced by groups that had higher initial levels. 2. The use of the X strain of distemper virus in the preparation of an influenza vaccine did not enhance the antigenicity of the influenza virus present. 3. Within certain limits the mean antibody response of human beings increased as the amount of virus injected was increased. When large amounts of influenza A virus were given, the antibody response was of the same order of magnitude as that which occurred following actual infection by this virus. 4. When the vaccine was prepared from allantoic fluid, there was no significant difference in the antibody response of human beings given active virus, formalin-inactivated virus, heat-inactivated virus, or virus inactivated by the drying process. 5. Ground infected chick embryos, when diluted with infected allantoic fluid, gave a greater antibody response than allantoic fluid alone (when the virus remained active). The antigenicity of such a preparation was diminished when the virus was inactivated by formalin. 6. Antibody levels 6 and 9 weeks after vaccination showed a marked drop from the 2-week postvaccination levels. In a small group the antibody levels at 5 months were still further reduced. Those individuals who possessed the higher titers tended to lose their antibodies faster than did those at a lower level.

scholarly journals STUDIES IN HUMAN IMMUNIZATION AGAINST INFLUENZA

1944 ◽  
Vol 80 (4) ◽  
pp. 265-273 ◽  
Author(s):  
G. K. Hirst ◽  
E. R. Rickard ◽  
W. F. Friedewald
Keyword(s):  
Influenza Virus ◽  
Antibody Response ◽  
Attack Rate ◽  
Influenza A ◽  
Allantoic Fluid ◽  
Great Majority ◽  
High Order ◽  
Human Beings ◽  
Antibody Levels ◽  
A Current

The administration to human beings of formalin-killed influenza virus, concentrated from allantoic fluid, resulted in a high order of antibody response within 2 weeks after injection. Even after 1 year the great majority of individuals vaccinated had antibody levels considerably above their prevaccination titer for the PR8, Lee, and a current 1943 strain. An investigation of the occurrence of epidemic influenza A in seven widely separated populations, 1 year after vaccination of part of these groups, showed that the attack rate among vaccinated persons was consistently lower than that of control individuals. The average reduction in attack rate was of the order of 35 per cent.

scholarly journals Haemagglutination-inhibiting (HI) antibodies against four prototype strains of influenza A virus in different age groups

1979 ◽  
Vol 82 (2) ◽  
pp. 225-230 ◽  
Author(s):  
A. L. Terzin ◽  
S. Djurišić ◽  
B. Vuković ◽  
V. Vujkov
Keyword(s):  
Influenza Virus ◽  
Hong Kong ◽  
New Jersey ◽  
Antibody Response ◽  
Influenza A ◽  
Geometric Mean ◽  
Age Groups ◽  
The Other ◽  
Younger Age ◽  
Lower Antibody Response

SUMMARYSera of 197 apparently well persons were tested for residual haemagglutination-inhibiting antibodies against live Hong Kong/68, A/FM/47 and A/PR/34 strains. Sera of 62 well persons, regularly exposed to contacts with swine, were tested against an inactivated A/New Jersey/76 antigen.Those born some time before and during a certain influenza era showed a significantly greater proportion of homologous residual titres against the subtype prevailing in that influenza era, than those born after the termination of the same era.In each of the seven age groups tested both the percentage of positives and the geometric mean titres were usually highest against the Hong Kong strain (representing the most recent era); the next highest were those against the FM1 strain and the lowest were those against the PR8 strain (representing the most distant of these three influenza eras).The serological involvement of donors exposed to regular contacts with swine was relatively stronger against the New Jersey antigen than the response of other serum donors shown against the other three, more recent, prototypes of influenza virus A. The oldest age groups showed significantly lower antibody response against the PR8, FM1 and Hong Kong strains (but not against the New Jersey antigen) than the next one or two of the younger age groups.

scholarly journals Antiviral Activity of Aspalathus linearis against Human Influenza Virus

2017 ◽  
Vol 12 (4) ◽  
pp. 1934578X1701200 ◽  
Author(s):  
Ratika Rahmasari ◽  
Takahiro Haruyama ◽  
Siriwan Charyasriwong ◽  
Tomoki Nishida ◽  
Nobuyuki Kobayashi
Keyword(s):  
Influenza Virus ◽  
Influenza A Virus ◽  
Influenza A ◽  
Time Course ◽  
Influenza Viruses ◽  
Replication Process ◽  
Human Influenza Virus ◽  
Alkaline Extract ◽  
Aspalathus Linearis

Influenza A viruses are responsible for annual epidemics and occasional pandemics, which cause significant morbidity and mortality. The limited protection offered by influenza vaccination, and the emergence of drug-resistant influenza strains, highlight the urgent need for the development of novel anti-influenza drugs. However, the search for antiviral substances from the library of low molecular weight chemical compounds is limited. Thus, because of their natural diversity and accessibility, plants or plant-derived materials are rapidly becoming valuable sources for the discovery and development of new antiviral drugs. In this study, crude extracts of Aspalathus linearis, a plant reported to have anti-HIV activity, were evaluated in vitro for their activity against the influenza A virus. Of the extracts tested, an alkaline extract of Aspalathus linearis demonstrated the strongest inhibition against influenza A virus and could also inhibit different types of influenza viruses, including Oseltamivir-resistant influenza viruses A and B. Our time course of addition studies indicated that the alkaline extract of Aspalathus linearis exerts its antiviral effect predominantly during the late stages of the influenza virus replication process.

scholarly journals N2Gas Plasma Inactivates Influenza Virus by Inducing Changes in Viral Surface Morphology, Protein, and Genomic RNA

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Akikazu Sakudo ◽  
Naohiro Shimizu ◽  
Yuichiro Imanishi ◽  
Kazuyoshi Ikuta
Keyword(s):  
Influenza Virus ◽  
Plasma Treatment ◽  
Influenza A ◽  
Allantoic Fluid ◽  
High Voltage Pulse ◽  
Influenza Viruses ◽  
Blue Staining ◽  
Enzyme Linked Immunosorbent Assay ◽  
Gas Plasma ◽  
Electron Microscopy Analysis

We have recently treated with N2gas plasma and achieved inactivation of bacteria. However, the effect of N2gas plasma on viruses remains unclear. With the aim of developing this technique, we analyzed the virucidal effect of N2gas plasma on influenza virus and its influence on the viral components. We treated influenza virus particles with inert N2gas plasma (1.5 kpps; kilo pulses per second) produced by a short high-voltage pulse generated from a static induction thyristor power supply. A bioassay using chicken embryonated eggs demonstrated that N2gas plasma inactivated influenza virus in allantoic fluid within 5 min. Immunochromatography, enzyme-linked immunosorbent assay, and Coomassie brilliant blue staining showed that N2gas plasma treatment of influenza A and B viruses in nasal aspirates and allantoic fluids as well as purified influenza A and B viruses induced degradation of viral proteins including nucleoprotein. Analysis using the polymerase chain reaction suggested that N2gas plasma treatment induced changes in the viral RNA genome. Scanning electron microscopy analysis showed that aggregation and fusion of influenza viruses were induced by N2gas plasma treatment. We believe these biochemical changes may contribute to the inactivation of influenza viruses by N2gas plasma.

scholarly journals A Novel Neuraminidase-Dependent Hemagglutinin Cleavage Mechanism Enables the Systemic Spread of an H7N6 Avian Influenza Virus

mBio ◽  
2019 ◽  
Vol 10 (6) ◽  
Author(s):  
Hyeok-il Kwon ◽  
Young-Il Kim ◽  
Su-Jin Park ◽  
Eun-Ha Kim ◽  
Semi Kim ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Avian Influenza ◽  
Influenza A ◽  
Systemic Infection ◽  
Influenza Viruses ◽  
Mallard Duck ◽  
Virulence Markers ◽  
Systemic Spread ◽  
Cleavage Motif

ABSTRACT In this study, we demonstrate a novel mechanism for hemagglutinin (HA) activation in a naturally occurring H7N6 avian influenza A virus strain, A/mallard duck/Korea/6L/2007 (A/Mdk/6L/07). This novel mechanism allows for systemic infection of chickens, ducks, and mice, and A/Mdk/6L/07 can replicate in vitro without exogenous trypsin and exhibits broad tissue tropism in animals despite the presence of a monobasic HA cleavage motif (PEIPKGR/G). The trypsin-independent growth phenotype requires the N6 neuraminidase and the specific recognition of glycine at the P2 position of the HA cleavage motif by a thrombin-like protease. Correspondingly, viral growth is significantly attenuated by the addition of a thrombin-like protease inhibitor (argatroban). These data provide evidence for a previously unrecognized virus replication mechanism and support the hypothesis that thrombin-mediated HA cleavage is an important virulence marker and potential therapeutic target for H7 influenza viruses. IMPORTANCE The identification of virulence markers in influenza viruses underpins risk assessment programs and the development of novel therapeutics. The cleavage of the influenza virus HA is a required step in the viral life cycle, and phenotypic differences in viruses can be caused by changes in this process. Here, we describe a novel mechanism for HA cleavage in an H7N6 influenza virus isolated from a mallard duck. The mechanism requires the N6 protein and full activity of thrombin-like proteases and allows the virus to cause systemic infection in chickens, ducks, and mice. The thrombin-mediated cleavage of HA is thus a novel virulence determinant of avian influenza viruses.

scholarly journals Ethanol Extract of Caesalpinia decapetala Inhibits Influenza Virus Infection In Vitro and In Vivo

Viruses ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 557 ◽  
Author(s):  
Li Zhang ◽  
Jungang Chen ◽  
Chang Ke ◽  
Haiwei Zhang ◽  
Shoujun Zhang ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
Antiviral Agents ◽  
Influenza Virus Infection ◽  
Virus Titer ◽  
Ethanol Extract ◽  
Influenza Viruses ◽  
Virus Infections

Influenza virus infections can lead to viral pneumonia and acute respiratory distress syndrome in severe cases, causing significant morbidity and mortality and posing a great threat to human health. Because of the diversity of influenza virus strains and drug resistance to the current direct antiviral agents, there have been no effective drugs as yet to cure all patients infected by influenza viruses. Natural products from plants contain compounds with diverse structures that have the potential to interact with multiple host and virus factors. In this study, we identified the ethanol extract of Caesalpinia decapetala (Roth) Alston (EEC) as an inhibitor against the replication of a panel of influenza A and B viruses both on human pulmonary epithelial A549 and human monocytic U937 cells. The animal study revealed that EEC administration reduces the weight loss and improves the survival rate of mice infected with lethal influenza virus. Also, EEC treatment attenuated lung injury and reduced virus titer significantly. In conclusion, we showed that EEC has antiviral activity both in vitro and in vivo, suggesting that the plant C. decapetala has the potential to be further developed as a resource of new anti-influenza drugs.

scholarly journals Kallikrein-Related Peptidase 5 Contributes to H3N2 Influenza Virus Infection in Human Lungs

2017 ◽  
Vol 91 (16) ◽  
Author(s):  
Mélia Magnen ◽  
Fabien Gueugnon ◽  
Antoine Guillon ◽  
Thomas Baranek ◽  
Virginie C. Thibault ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Respiratory Tract ◽  
Serine Proteases ◽  
Lower Respiratory Tract ◽  
Influenza A ◽  
Seasonal Influenza ◽  
Influenza Viruses ◽  
H3n2 Virus ◽  
Influenza A Viruses

ABSTRACT Hemagglutinin (HA) of influenza virus must be activated by proteolysis before the virus can become infectious. Previous studies indicated that HA cleavage is driven by membrane-bound or extracellular serine proteases in the respiratory tract. However, there is still uncertainty as to which proteases are critical for activating HAs of seasonal influenza A viruses (IAVs) in humans. This study focuses on human KLK1 and KLK5, 2 of the 15 serine proteases known as the kallikrein-related peptidases (KLKs). We find that their mRNA expression in primary human bronchial cells is stimulated by IAV infection. Both enzymes cleaved recombinant HA from several strains of the H1 and/or H3 virus subtype in vitro, but only KLK5 promoted the infectivity of A/Puerto Rico/8/34 (H1N1) and A/Scotland/20/74 (H3N2) virions in MDCK cells. We assessed the ability of treated viruses to initiate influenza in mice. The nasal instillation of only the KLK5-treated virus resulted in weight loss and lethal outcomes. The secretion of this protease in the human lower respiratory tract is enhanced during influenza. Moreover, we show that pretreatment of airway secretions with a KLK5-selective inhibitor significantly reduced the activation of influenza A/Scotland/20/74 virions, providing further evidence of its importance. Differently, increased KLK1 secretion appeared to be associated with the recruitment of inflammatory cells in human airways regardless of the origin of inflammation. Thus, our findings point to the involvement of KLK5 in the proteolytic activation and spread of seasonal influenza viruses in humans. IMPORTANCE Influenza A viruses (IAVs) cause acute infection of the respiratory tract that affects millions of people during seasonal outbreaks every year. Cleavage of the hemagglutinin precursor by host proteases is a critical step in the life cycle of these viruses. Consequently, host proteases that activate HA can be considered promising targets for the development of new antivirals. However, the specific proteases that activate seasonal influenza viruses, especially H3N2 viruses, in the human respiratory tract have remain undefined despite many years of work. Here we demonstrate that the secreted, extracellular protease KLK5 (kallikrein-related peptidase 5) is efficient in promoting the infectivity of H3N2 IAV in vitro and in vivo. Furthermore, we found that its secretion was selectively enhanced in the human lower respiratory tract during a seasonal outbreak dominated by an H3N2 virus. Collectively, our data support the clinical relevance of this protease in human influenza pathogenesis.

scholarly journals Zanamivir, at 600 Milligrams Twice Daily, Inhibits Oseltamivir-Resistant 2009 Pandemic H1N1 Influenza Virus in anIn VitroHollow-Fiber Infection Model System

2011 ◽  
Vol 55 (4) ◽  
pp. 1740-1746 ◽  
Author(s):  
Ashley N. Brown ◽  
James J. McSharry ◽  
Qingmei Weng ◽  
Jonathan R. Adams ◽  
Robert Kulawy ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
H1n1 Influenza ◽  
Model System ◽  
Hospitalized Patients ◽  
Influenza Viruses ◽  
Infection Model ◽  
Pandemic H1n1 ◽  
The Government

ABSTRACTIn 2009, a novel H1N1 influenza A virus emerged and spread worldwide, initiating a pandemic. Various isolates obtained from disparate parts of the world were shown to be uniformly resistant to the adamantanes but sensitive to the neuraminidase inhibitors oseltamivir and zanamivir. Over time, resistance to oseltamivir became more prevalent among pandemic H1N1 virus isolates, while most remained susceptible to zanamivir. The government has proposed the use of intravenous (i.v.) zanamivir to treat serious influenza virus infections among hospitalized patients. To use zanamivir effectively for patients with severe influenza, it is necessary to know the optimal dose and schedule of administration of zanamivir that will inhibit the replication of oseltamivir-sensitive and -resistant influenza viruses. Therefore, we performed studies using thein vitrohollow-fiber infection model system to predict optimal dosing regimens for zanamivir against an oseltamivir-sensitive and an oseltamivir-resistant virus. Our results demonstrated that zanamivir, at a dose of 600 mg given twice a day (Q12h), inhibited the replication of oseltamivir-sensitive and oseltamivir-resistant influenza viruses throughout the course of the experiment. Thus, our findings suggest that intravenous zanamivir, at a dose of 600 mg Q12h, could be used to treat hospitalized patients suffering from serious infections with oseltamivir-sensitive or -resistant influenza viruses.

scholarly journals The Magnitude and Specificity of Influenza A Virus-Specific Cytotoxic T-Lymphocyte Responses in Humans Is Related to HLA-A and -B Phenotype

2002 ◽  
Vol 76 (2) ◽  
pp. 582-590 ◽  
Author(s):  
A. C. M. Boon ◽  
G. de Mutsert ◽  
Y. M. F. Graus ◽  
R. A. M. Fouchier ◽  
K. Sintnicolaas ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A Virus ◽  
Influenza A ◽  
Influenza Viruses ◽  
Hla B27 ◽  
Ctl Response ◽  
Restricted Epitope ◽  
Ctl Activity ◽  
Hla Molecules

ABSTRACT The repertoire of human cytotoxic T-lymphocytes (CTL) in response to influenza A viruses has been shown to be directed towards multiple epitopes, with a dominant response to the HLA-A2-restricted M158–66 epitope. These studies, however, were performed with peripheral blood mononuclear cells (PBMC) of individuals selected randomly with respect to HLA phenotype or selected for the expression of one HLA allele without considering an influence of other HLA molecules. In addition, little information is available on the influence of HLA makeup on the overall CTL response against influenza viruses. Here, the influenza A virus-specific CTL response was investigated in groups of HLA-A and -B identical individuals. Between groups the individuals shared two or three of the four HLA-A and -B alleles. After in vitro stimulation of PBMC with influenza virus, the highest CTL activity was found in HLA-A2+ donors. A similar pattern was observed for the precursor frequency of virus-specific CTL (CTLp) ex vivo, with a higher CTLp frequency in HLA-A2-positive donors than in HLA-A2-negative donors, which were unable to recognize the immunodominant M158–66 epitope. In addition, CTL activity and frequency of CTLp for the individual influenza virus epitopes were determined. The frequency of CTLp specific for the HLA-B8-restricted epitope NP380–388 was threefold lower in HLA-B27-positive donors than in HLA-B27-negative donors. In addition, the frequency of CTLp specific for the HLA-A1-restricted epitope NP44–52 was threefold higher in HLA-A1-, -A2-, -B8-, and -B35-positive donors than in other donors, which was confirmed by measuring the CTL activity in vitro. These findings indicate that the epitope specificity of the CTL response is related to the phenotype of the other HLA molecules. Furthermore, the magnitude of the influenza virus-specific CTL response seems dependent on the HLA-A and -B phenotypes.

scholarly journals Evaluation of Influenza Virus A/H3N2 and B Vaccines on the Basis of Cross-Reactivity of Postvaccination Human Serum Antibodies against Influenza Viruses A/H3N2 and B Isolated in MDCK Cells and Embryonated Hen Eggs

2012 ◽  
Vol 19 (6) ◽  
pp. 897-908 ◽  
Author(s):  
Noriko Kishida ◽  
Seiichiro Fujisaki ◽  
Masaru Yokoyama ◽  
Hironori Sato ◽  
Reiko Saito ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Human Serum ◽  
Neutralizing Antibodies ◽  
Influenza A ◽  
Geometric Mean ◽  
Cross Reactivity ◽  
Influenza Viruses ◽  
Serum Antibodies ◽  
Influenza Virus A ◽  
The Cross

ABSTRACTThe vaccine strains against influenza virus A/H3N2 for the 2010-2011 season and influenza virus B for the 2009-2010 and 2010-2011 seasons in Japan are a high-growth reassortant A/Victoria/210/2009 (X-187) strain and an egg-adapted B/Brisbane/60/2008 (Victoria lineage) strain, respectively. Hemagglutination inhibition (HI) tests with postinfection ferret antisera indicated that the antisera raised against the X-187 and egg-adapted B/Brisbane/60/2008 vaccine production strains poorly inhibited recent epidemic isolates of MDCK-grown A/H3N2 and B/Victoria lineage viruses, respectively. The low reactivity of the ferret antisera may be attributable to changes in the hemagglutinin (HA) protein of production strains during egg adaptation. To evaluate the efficacy of A/H3N2 and B vaccines, the cross-reactivities of postvaccination human serum antibodies against A/H3N2 and B/Victoria lineage epidemic isolates were assessed by a comparison of the geometric mean titers (GMTs) of HI and neutralization (NT) tests. Serum antibodies elicited by the X-187 vaccine had low cross-reactivity to both MDCK- and egg-grown A/H3N2 isolates by HI test and narrow cross-reactivity by NT test in all age groups. On the other hand, the GMTs to B viruses detected by HI test were below the marginal level, so the cross-reactivity was assessed by NT test. The serum neutralizing antibodies elicited by the B/Brisbane/60/2008 vaccine reacted well with egg-grown B viruses but exhibited remarkably low reactivity to MDCK-grown B viruses. The results of these human serological studies suggest that the influenza A/H3N2 vaccine for the 2010-2011 season and B vaccine for the 2009-2010 and 2010-2011 seasons may possess insufficient efficacy and low efficacy, respectively.

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