Dna Vec Research Inc.

Japan, As Represented by the Director-general of National Institute of Infectious Disease

Yoshiyuki Nagai

Mamoru Hasegawa

Atsushi Kato

Tatsuo Shioda

Tsuneaki Sakata

Fukashi Murai

Makoto Asakawa

Makoto Inoue

Akihiro Iida

Tetsuro Matano

Tsuyoshi Tokusumi

Munehide Kano

Chikaya Moriya

The present invention provides a vaccine containing a Sendai virus vector encoding a virus protein of an immunodeficiency virus. By intranasally administering a Sendai virus encoding a virus protein of an immunodeficiency virus to a macaque monkey, the present inventors have succeeded in efficiently inducing protective immunity against an immunodeficiency virus. As a result of intranasal inoculation of vaccine, expression of an antigen protein mediated by Sendai virus vector was detected in intranasal mucous membrane and local lymph nodes and antigen-specific cellular immune response was induced at a significant level. No pathological symptom by vaccination was observed. After vaccination, exposure of simian immunodeficiency virus was performed and the effect was examined. As a result, the amount of virus in plasma significantly decreased, compared with that of the control animal. The present invention provides a promising vaccine as an AIDS vaccine.

AIDS virus vaccines using Sendai virus vector

A method for regenerating Sendai virus particles by transfecting the Sendai virus genome to a host expressing all genes for the initial viral replication has been developed, enabling the genetic manipulation of Sendai virus and effective utilization of said virus as the vector.

Recombinant sendai virus

The present invention provides virus vectors of the family Paramyxoviridae in which the transcription start (S) sequence has been modified so as to modify the expression of genes located downstream thereof, a method for producing the vectors, and uses thereof. By measuring the transcription initiation efficiency of the S sequence of each gene carried by Sendai viruses (SeV), it was clarified that the S sequence of F gene has a significantly lower ability to promote transcription than the other three S sequences. When the S sequence of the F gene of wild type Sendai virus was substituted by the S sequence of the P/M/HN gene-type showing a high transcription initiation efficiency, the F gene of the resultant Sendai virus mutant and genes located downstream thereof show elevated expression levels. It was also revealed that this mutant proliferates more quickly than the wild type. The vectors of this invention are useful in elevating the expression of foreign genes and producing pharmaceutical compositions and vaccines. Furthermore, by lowering virus gene expression from virus vectors, it is possible to suppress transcription and/or replication and reduce cytotoxicity of the vector genome.

Paramyxoviruses comprising modified transcription start sequence

A method for generating Sendai virus particles by transfecting the Sendai virus genome to a host expressing all genes for the initial viral replication has been developed, enabling the genetic manipulation of Sendai virus and effective utilization of said virus as the vector.

Recombinant Sendai virus

A recombinant Sendai virus vector expressing chemokine is provided. This vector enables large quantity production of clinically useful chemokines. It is also useful for treatment of diseases that can be treated by chemokines.

Recombinant sendai virus vector including a gene encoding a chemokine

A paramyxovirus vector capable of Extransfecting foreign genes and having a replication capacity, is provided. A Sendai virus vector comprising a foreign gene can be constructed by inserting a foreign gene between the viral genes of the Sendai virus genome. These Sendai viruses have a replication capacity and express the foreign gene in transfected cells. The expression level of the foreign gene is higher towards the 3&prime; end of negative strand RNA, and especially, a high level of expression is obtained when the foreign gene is inserted before the NP gene, and between P gene and M gene. Conversely, the expression decreases towards 5&prime; end of negative strand RNA, and especially, a relatively low level of expression is obtained when the when the foreign gene is inserted between HN gene and L gene, and between F gene and HN gene. Thus, the vector of the invention enables the regulation of the expression level of a foreign gene. The vector is useful for gene therapy due to its safety, high gene transfer efficiency, and capacity to express a foreign gene at a high level.

Paramyxovirus vectors used for transfer of foreign genes

A method for reconstituting Sendai viral particles by transfecting Sendai virus to a host expressing all genes for the initial replication has been developed, enabling the Production of negative strand RNA vectors highly useful for practical applications.

Negative strand RNA viral vector having autonomous replication capability

A method for reconstituting Sendai viral particles by transfecting Sendai virus to a host expressing all genes for the initial replication has been developed, enabling the production of negative strand RNA vectors highly useful for practical applications.

Growing community of inventors

Toyama, Japan

Yoshiyuki Nagai