scholarly journals A COMPLEX VACCINE AGAINST INFLUENZA A VIRUS

1941 ◽  
Vol 73 (3) ◽  
pp. 335-355 ◽  
Author(s):  
Frank L. Horsfall ◽  
Edwin H. Lennette ◽  
Elsmere R. Rickard

A quantitative study of the antigenicity of various vaccines containing influenza A virus has been made in human beings. A complex vaccine prepared from chick embryos inoculated with both influenza A virus and the X strain of canine distemper virus was found to be more effective than other vaccines in stimulating the production of neutralizing antibodies against the former virus. The increased antibody levels which resulted from the administration of this vaccine remained almost unaltered for at least 5 months.

1941 ◽  
Vol 74 (5) ◽  
pp. 433-439 ◽  
Author(s):  
F. L. Horsfall ◽  
E. R. Rickard

The increased concentrations of neutralizing antibodies against influenza A virus in human serum which occur after influenza A do not differentiate between antigenically different strains of this virus or swine influenza virus but instead appear to possess equal reactivity against these agents. The decrease in antibody levels which occurs with time is also independent of the strain of virus used to measure it.


2016 ◽  
Vol 113 (42) ◽  
pp. 11931-11936 ◽  
Author(s):  
Wenqian He ◽  
Gene S. Tan ◽  
Caitlin E. Mullarkey ◽  
Amanda J. Lee ◽  
Mannie Man Wai Lam ◽  
...  

The generation of strain-specific neutralizing antibodies against influenza A virus is known to confer potent protection against homologous infections. The majority of these antibodies bind to the hemagglutinin (HA) head domain and function by blocking the receptor binding site, preventing infection of host cells. Recently, elicitation of broadly neutralizing antibodies which target the conserved HA stalk domain has become a promising “universal” influenza virus vaccine strategy. The ability of these antibodies to elicit Fc-dependent effector functions has emerged as an important mechanism through which protection is achieved in vivo. However, the way in which Fc-dependent effector functions are regulated by polyclonal influenza virus-binding antibody mixtures in vivo has never been defined. Here, we demonstrate that interactions among viral glycoprotein-binding antibodies of varying specificities regulate the magnitude of antibody-dependent cell-mediated cytotoxicity induction. We show that the mechanism responsible for this phenotype relies upon competition for binding to HA on the surface of infected cells and virus particles. Nonneutralizing antibodies were poor inducers and did not inhibit antibody-dependent cell-mediated cytotoxicity. Interestingly, anti-neuraminidase antibodies weakly induced antibody-dependent cell-mediated cytotoxicity and enhanced induction in the presence of HA stalk-binding antibodies in an additive manner. Our data demonstrate that antibody specificity plays an important role in the regulation of ADCC, and that cross-talk among antibodies of varying specificities determines the magnitude of Fc receptor-mediated effector functions.


2008 ◽  
Vol 83 (1) ◽  
pp. 65-72 ◽  
Author(s):  
Zhongying Chen ◽  
Celia Santos ◽  
Amy Aspelund ◽  
Laura Gillim-Ross ◽  
Hong Jin ◽  
...  

ABSTRACT Avian influenza A virus A/teal/HK/W312/97 (H6N1) possesses seven gene segments that are highly homologous to those of highly pathogenic human influenza H5N1 viruses, suggesting that a W312-like H6N1 virus might have been involved in the generation of the A/HK/97 H5N1 viruses. The continuous circulation and reassortment of influenza H6 subtype viruses in birds highlight the need to develop an H6 vaccine to prevent potential influenza pandemics caused by the H6 viruses. Based on the serum antibody cross-reactivity data obtained from 14 different H6 viruses from Eurasian and North American lineages, A/duck/HK/182/77, A/teal/HK/W312/97, and A/mallard/Alberta/89/85 were selected to produce live attenuated H6 candidate vaccines. Each of the H6 vaccine strains is a 6:2 reassortant ca virus containing HA and NA gene segments from an H6 virus and the six internal gene segments from cold-adapted A/Ann Arbor/6/60 (AA ca), the master donor virus that is used to make live attenuated influenza virus FluMist (intranasal) vaccine. All three H6 vaccine candidates exhibited phenotypic properties of temperature sensitivity (ts), ca, and attenuation (att) conferred by the internal gene segments from AA ca. Intranasal administration of a single dose of the three H6 ca vaccine viruses induced neutralizing antibodies in mice and ferrets and fully protected mice and ferrets from homologous wild-type (wt) virus challenge. Among the three H6 vaccine candidates, the A/teal/HK/W312/97 ca virus provided the broadest cross-protection against challenge with three antigenically distinct H6 wt viruses. These data support the rationale for further evaluating the A/teal/HK/W312/97 ca vaccine in humans.


Viruses ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 688 ◽  
Author(s):  
Miguel Angel Muñoz-Alía ◽  
Stephen J. Russell

Measles virus (MeV) is monotypic. Live virus challenge provokes a broadly protective humoral immune response that neutralizes all known measles genotypes. The two surface glycoproteins, H and F, mediate virus attachment and entry, respectively, and neutralizing antibodies to H are considered the main correlate of protection. Herein, we made improvements to the MeV reverse genetics system and generated a panel of recombinant MeVs in which the globular head domain or stalk region of the H glycoprotein or the entire F protein, or both, were substituted with the corresponding protein domains from canine distemper virus (CDV), a closely related morbillivirus that resists neutralization by measles-immune sera. The viruses were tested for sensitivity to human or guinea pig neutralizing anti-MeV antisera and to ferret anti-CDV antisera. Virus neutralization was mediated by antibodies to both H and F proteins, with H being immunodominant in the case of MeV and F being so in the case of CDV. Additionally, the globular head domains of both MeV and CDV H proteins were immunodominant over their stalk regions. These data shed further light on the factors constraining the evolution of new morbillivirus serotypes.


2008 ◽  
Vol 52 (No. 2) ◽  
pp. 69-73 ◽  
Author(s):  
L. Pavlacik ◽  
V. Celer ◽  
P. Koubek ◽  
I. Literak

Between 2001 and 2003, a total of 194 samples of brain tissues of wild mustelids from the Czech Republic were tested for the presence of canine distemper virus (CDV) by direct immunofluorescence examination. Out of 21 animals exhibiting symptoms of the disease or changed behaviour, one mustelid was CDV positive (5% prevalence). In this group, 1 out of 18 stone martens (<i>Martes foina</i>) was CDV positive, while 2 pine martens (<i>Martes martes</i>) and 1 Eurasian badger (<i>Meles meles</i>) were CDV negative. Of 173 animals with unknown case history, 1 sample was positive (0.6% prevalence). In this group of animals, 1 out of 19 Eurasian badgers was positive, and stone martens (<i>n</i> = 96), pine martens (<i>n</i> = 4), polecats (<i>Mustela putorius</i>) ((<i>n</i> = 28), steppe polecats (<i>Mustela eversmani</i>) (<i>n</i> = 4), common weasels (<i>Mustela nivalis</i>) (<i>n</i> = 4), stoats (<i>Mustela erminea</i>) (<i>n</i> = 3) and American minks (<i>Mustela vison</i>) (<i>n</i> = 19) were negative. Clinical distemper was demonstrated in three stone marten pup siblings. In two of the siblings, CDV was demonstrated in footpads. The third of the siblings survived the acute stage of the disease and had virus neutralizing antibodies from the end of the acute stage until 6 months after the end of the acute stage, with a maximum antibody titre of 32. During the acute stage and 7 months after the end of the acute stage, no virus neutralizing antibodies were found.


1949 ◽  
Vol 90 (4) ◽  
pp. 321-334 ◽  
Author(s):  
Robert R. Wagner ◽  
Ivan L. Bennett ◽  
Virgil S. LeQuire

The intravenous injection of the PR8 strain of influenza A virus, the Lee strain of influenza B, and the "B" strain of Newcastle disease virus produces fever in rabbits. This phenomenon has been studied in relation to certain in vitro properties of these viruses. Saline suspensions of virus prepared by centrifugation or elution from chicken erythrocytes produced fever. Fluids from which most of the virus particles had been removed were non-pyrogenic. Exposure to temperatures which destroyed the infectivity of the virus for chick embryos did not prevent fever. However, heating sufficient to destroy the hemagglutinin also rendered virus non-pyrogenic. The injection of erythrocytes onto which virus had been adsorbed produced fever. Heated virus adsorbed onto erythrocytes, which failed to elute, produced no elevation of temperature, although heated virus alone was pyrogenic. Neutralization of virus with specific immune serum prevented fever. Antipyrine was capable of abolishing the febrile response to virus. Certain differences between the febrile response in rabbits to the injection of viruses and that following bacterial pyrogens were noted. The period between injection and beginning of temperature rise is longer with virus than with bacterial pyrogens. Relatively low temperatures inactivate the fever-producing capacity of viruses, whereas bacterial pyrogens withstand prolonged autoclaving, and the neutralization of viral fever by specific immune serum contrasts sharply with the failure of antibody to affect the response to bacterial pyrogens. Certain previous observations on the lymphopenia produced in rabbits by the injection of influenzal viruses were confirmed. The capacity of virus preparations to induce fever in rabbits closely parallels their capacity to induce lymphopenia. It was concluded that the fever-producing property of influenzal viruses is closely associated with the capacity to agglutinate erythrocytes.


2004 ◽  
Vol 71 (3) ◽  
Author(s):  
O.I. Oyedele ◽  
D.O. Oluwayelu ◽  
S.I.B. Cadmus ◽  
F.D. Adu

Blood samples from 50 dogs were collected at three veterinary clinics in Ibadan and Abuja, Nigeria and the serum from each sample was evaluated serologically for neutralizing antibodies against canine distemper virus (CDV) by the highly sensitive plaque reduction (PRN) neutralization assay. Thirteen dogs had plaque reduction neutralization titres of 0-100, seven had titres of 100-1 000 while 30 had titres ranging from 1 000-6 000. The PRN titres of vaccinated dogs were found to be significantly higher than unvaccinated dogs. The widespread use of the highly reproducible PRN test for the evaluation of antibody response to CDV may be very important in the generation of international CDV positive serum standards that should help to improve pre-and post-vaccination testing of dogs worldwide.


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