Immunisation with canarypox virus expressing rabies glycoprotein
Autor: | J. Taylor, M Cadoz, A Strady, J Tartaglia, Scott R. Plotkin, Enzo Paoletti, Bernard Meignier |
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Rok vydání: | 1992 |
Předmět: |
Adult
Male Canarypox Canaries Rabies Genetic Vectors Canarypox virus Booster dose Antibodies Viral Virus chemistry.chemical_compound Viral Envelope Proteins Neutralization Tests medicine Animals Humans Antigens Viral Duck embryo vaccine Glycoproteins Vaccines Synthetic biology Poxviridae General Medicine Middle Aged biology.organism_classification medicine.disease Virology Vaccination chemistry Rabies Vaccines Immunology Female Vaccinia |
Zdroj: | Lancet (London, England). 339(8807) |
ISSN: | 0140-6736 |
Popis: | Poxviruses have many useful features as vectors for genes that carry immunising antigens from other viruses, such as ease of production and induction of cellular and humoral immunity, but there is concern about the safety of vaccinia virus. We turned to an avian poxvirus (canarypox); this virus undergoes abortive replication in mammalian cells that enables presentation of early gene products to the immune system. Canarypox virus was used as a vector for the rabies glycoprotein G gene. The safety and efficacy of the recombinant (ALVAC-RG; vCP65) were tested in several animal species, then it was subjected to a phase 1 clinical trial. Twenty-five volunteers were randomly assigned to subcutaneous injections of the recombinant (three groups [A, B, and C] received two doses each of 10(3.5), 10(4.5), and 10(5.5) tissue-culture infectious doses50, respectively) or of human diploid cell culture vaccine (HDC; 6.52 international potency units per dose). 28 days after the second dose, all nine ALVAC-RG group-C subjects and two of three group-B subjects had rabies neutralising antibody concentrations of at least 0.5 IU/ml, the level associated with protection in animals. Although the geometric mean titre of these antibodies at that time was lower in group C than in the ten HDC recipients (4.4 [range 0.9-12.5] vs 11.5 [4.7-25.3] IU/ml), a single booster dose at 6 months induced a recall response in volunteers primed with either vaccine. Side-effects associated with ALVAC-RG were mild and of short duration and occurred at similar frequency to those of HDC vaccine. This study has shown the potential of non-replicating poxviruses as vectors for vaccination in human beings. Trials of canarypox-virus recombinants at higher doses and by other routes of administration are needed. |
Databáze: | OpenAIRE |
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