Issue |
Vet. Res.
Volume 31, Number 1, January-February 2000
|
|
---|---|---|
Page(s) | 135 - 136 | |
DOI | https://doi.org/10.1051/vetres:2000028 | |
How to cite this article | Vet. Res. (2000) 135-136 |
Genetically improved Aujeszky's disease strain MNC+/10a derived from strain K/61 and testing for safety and potency in pigs
B. Lomniczia, M. Kelemenb and E. Wehmannaa Veterinary Medical Research Institute, Hungarian Academy of Sciences 1143 Budapest, Hungaria krt. 21., Hungary
b Phylaxia-Sanofi Ltd. A Company of SSNA, Budapest, Hungary
Abstract -
Aujeszky's
disease vaccine strain Bartha K/61 carries at least two genetic defects that
can be deleterious in a vaccine strain. It is deficient in the expression of glycoprotein gC,
a protective antigen of the virus and its gM lacks carbohydrate side chains.
Both glycoproteins are necessary for optimal growth, therefore the antigenicity of a live
vaccine that is deficient in these functions, must be impaired in vivo. Our aim
was to restore the function of glycoprotein gC in order to obtain an attenuated strain with
improved immunogenicity. In order to correct the defects of K/61, a mixed infection
of K/61 and a virulent strain was performed to generate recombinants. From the offspring, a
recombinant (designated MNC+/10a) was selected in which the essential properties
of vaccine strain K/61, such as the defects of its major virulence gene (UL21) and the lack
of gE gene were retained. Three week-old piglets inoculated intranasally with
107 plaque forming units of MNC+/10a remained healthy and the mutant proved to be avirulent
in day-old chickens injected intracerebrally. A restriction site marker
(BamHI 2a+2b) was also transferred from the virulent parent to the avirulent MNC+/10a strain
together with an adjacent region that carries the gC gene. As detected by a
gC-specific monoclonal antibody MNC+/10a was gC-positive (Dr. T.C. Mettenleiter, personal
communication). It is possible that gM was also rescued because MNC+/10a
forms larger plaques than K/61. In addition, MNC+/10a showed a ten-fold higher growth
capacity in the nasal mucosa of piglets as compared to K/61. The immunogenicity
of MNC+/10a was tested in pigs in a standard challenge experiment. Upon intramuscular
injection, MNC+/10a induced significantly higher antibody levels than K/61.
Groups of pigs free from Aujeszky-disease virus antibodies were vaccinated once or twice with
Aujeszky- vaccine Auphyl-plus (Phylaxia-Sanofi) that contains the attenuated
strain MNC+/10a with an oil/water emulsion adjuvant. Three weeks after the first or second
injection the pigs were challenged intranasally with
104 PFU of the virulent strain
NIA-3 in two separate experiments. Most unvaccinated animals showed severe respiratory and
nervous signs on postinfection days 4 to 6 and the average daily weight gains were reduced to
about
in the control groups. Altogether, ten of the twelve control animals
succumbed to
the challenge infection. A single dose of the vaccine was sufficient to prevent
disease but did not prevent mild
fever and transient (1-2 days) anorexia in some
animals. Two doses of the vaccine prevented both. The average daily weight gains
of the once and twice vaccinated groups were 1.47% and 0.90%, respectively as compared to the
weight loss of
in the unvaccinated pigs. Virus shedding measured by total
excreted virus was significantly reduced (150 times) in the twice-vaccinated group as
compared to controls. To simulate natural conditions of virus spread, pigs
vaccinated twice were placed in the pens of twice vaccinated, intranasally challenged
animals. None of the contact-challenged vaccinated pigs shed virus during a
two-week observation period. There was a positive correlation between the ability of the
vaccine strain to replicate in the nasal mucosa and the primary antibody response
in pigs. This is the first report demonstrating that the restoration of a protective protein
function has indeed resulted in an improved antigenicity as measured by an elevated
level of antibody production. The vaccine prepared from the virus strain ensures excellent
protection against the clinical signs and virus shedding.
Corresponding author: B. Lomniczi Tel.: (36) 1 467 4069; fax: (36) 1 252 1069;
e-mail: lomniczi@novell.vmri.hu
© INRA, EDP Sciences 2000