IMMUNE RESPONSE AGAINST VIRAL ANTIGEN IN IMMUNE COMPLEX
Main researcher
: POKRIĆ, BISERKA (37830) Assistants
BIĐIN, ZDENKO (3545)
ČAJAVEC, STANISLAV (7575)
JUROŠ, SUZANA (153566)
Type of research: basic Duration from: 01/01/91. to 12/31/96. Papers on project (total): 5
Institution name: Institut "Ruđer Bošković", Zagreb (98) Department/Institute: Center for marine research - Zagreb Address: Bijenička 54 City: 10000 - Zagreb, Croatia
Communication
Phone: 385 (0)1 425-459
Fax: 385 (0)1 425-497
E-mail: pokric@olimp.irb.hr
Summary: BACKGROUND AND PURPOSE: Vaccination is still the best way
for prevention of viral diseases. Undesirable side-effects, accompanying
vaccines prepared from whole viruses, are avoided by the use of the
antigenic viral subunits. Viral subunits are mainly poor immunogens.
Antigen bound in an immune complex (IC) with specific antibodies elicts an
enhanced immune response rather than antigen alone.
RESULTS: The methods and techniques for identification and
analysis od viruses and viral antigenic subunits and specific
virus-neutralizing antibodies are developed and applied. The
conditions for the preparation of the viral antigens of intact natural
composition and conformation, were determined. The conditions for the
IC preparation at equivalence were found. It was proved that antigen
(HSA) bound at equivalence to the specific antibodies in IC, elicited
enhanced humoral and cellular immune responses rather than free antigen. A
better understanding of the mechanism of immune responses against an
antigen in IC, contributes to a more rational design of subunit vaccines
based on ICs. An IC, composed of
antigenic subunits of Newcastle disease virus (NDV) and specific
polyclonal chicken antibodies, was prepared. The NDV is used as a model
for the preparation of vaccines based on ICs, since it belongs to a
wide-spread family of enveloped viruses causing numerous human and animal
diseases. Laboratory and field experiments, using chickens as experimental
animals, proved that a very low quantities of the viral material in the IC
generated protective level of the specific antibodies and the protection
against infection. The efficiency of numerous viral vaccines, especially
those used for the poultry protection and composed of the viral particles
as well as viral subunits, was simultaneously determined. CONCLUSIONS:
Pure viral subunits of molecularly defined composition can be easily
prepared by binding to the specific antibodies in ICs. The IC vaccines
represent a progress towards safe and ecologically convenient vaccine and
provide a modern orientation to the use of combined vaccines. Our results
and literature data agree that viral antigens coupled to specific
antibodies are efficiently presented to the immunological system thus
eliciting an enhanced immune response.
Research goals: The aims of this work are: (i) the studies of
humoral and cellular immune responses against antigens and viral antigenic
subunits bound in the IC and the role of the IC in the defense against
"non-self", (ii) comparison of humoral and cellular immune responses as
well as efficiency of immune protection against viruses generated by viral
subunits bound in IC, free subunits and whole viral particles, (iii)
comparison of humoral and cellular immune responses and efficiency of
immune protection against viral infection generated by viral antigenic
subunits coupled to specific antibodies in IC and viral antigenic subunits
inoculated in appropriate adjuvants. These studies, together with our
results showing the enhanced immune responses triggered by antigen in IC,
may lead to the development of a new generation of vaccines. Vaccination
is the only efficient way of preventing of viral diseases. The best immune
protection is generated by vaccines containing inactivated or attenuated
viruses. However, their application could be accompanied with undesirable
side-effects. So far, attenuated vaccines are environmentally inconvenient.
For these reasons, the vaccines containing antigenic viral subunits instead
of viral particles were introduced. The poor immunogenicity of subunit
vaccines is the barrier of widespread use of them. Our studies confirm
that viral subunits coupled to the specific antibodies in an insoluble IC,
without addition of adjuvants or immune stimulators, elicit the
appropriate immune responses and anti-viral protection. The IC is
environmentally safe and does not generate undesirable side-effects.
Simultaneously with the poultry vaccines, other animal (rabies) or human
anti-viral vaccines based on ICs, may be developed. In this case, new
technology in vaccine production can be designed and introduced. Other information about the project.