Title:  DNA immunization against chlamydia infection

United States Patent:  6,235,290

Assignee:   University of Manitoba (Winnipeg, CA)

Filed:  July 11, 1997

Nucleic acid, including DNA, immunization to generate a protective immune response in a host, including humans, to a major outer membrane protein of a strain of Chlamydia, preferably contains a nucleotide sequence encoding a MOMP or a MOMP fragment that generates antibodies that specifically react with MOMP and a promoter sequence operatively coupled to the first nucleotide sequence for expression of the MOMP in the host. The non-replicating vector may be formulated with a pharmaceutically-acceptable carrier for in vivo administration to the host.

SUMMARY OF THE INVENTION

The present invention is concerned with nucleic acid immunization, specifically DNA immunization, to generate in a host protective antibodies to a MOMP of a strain of Chlamydia. DNA immunization induces a broad spectrum of immune responses including TH1-like CD4 responses and mucosal immunity.

Accordingly, in one aspect, the present invention provides an immunogenic composition in vivo for in vivo administration to a host for the generation in the host of a protective immune response to a major outer membrane protein (MOMP) of a strain of Chlamydia, comprising a non-replicating vector comprising a nucleotide sequence encoding a MOMP or MOMP fragment that generates a MOMP-specific immune response, and a promoter sequence operatively coupled to said nucleotide sequence for expression of said MOMP in the host; and a pharmaceutically-acceptable carrier therefor.

The nucleotide sequence may encode a full-length MOMP protein or may encode a fragment, such as the N-terminal half of MOMP. The nucleotide sequence may encode a MOMP which stimulates a recall immune response following exposure to wild-type Chlamydia. The promoter may be the cytomegalovirus promoter.

The strain of Chlamydia may be a strain of Chlamydia inducing chlamydial infection of the lung, including Chalamydia trachomatis or Chalamydia pneumoniae. The non-replicating vector may be plasmid pcDNA3 into which the nucleotide sequence is inserted. The immune response which is stimulated may be predominantly a cellular immune response.

In a further aspect of the invention, there is provided as a method of immunizing a host against disease caused by infection with a strain of Chlamydia, which comprises administering to said host an effective amount of a non-replicating vector comprising a nucleotide sequence encoding a major outer membrane protein (MOMP) of a strain of Chlamydia or a MOMP fragment that generates a MOMP-specific immune response, and a promoter sequence operatively coupled to said nucleotide sequence for expression of said MOMP in the host.

In this aspect of the present invention, the various options and alternatives discussed above may be employed.

The non-replicating vector may be administrated to the host, including a human host, in any convenient manner, such as intramuscularly or intranasally. Intranasal administration stimulated the strongest immune response in experiments conducted herein.

The present invention also includes, in an additional aspect thereof, there is provided a method of using a gene encoding a major outer membrane protein (MOMP) of a strain of Chlamydia or MOMP fragment that generates a MOMP-specific immune response, to produce an immune response in a host, which comprises: isolating said gene, operatively linking said gene to at least one control sequence to produce a non-replicating vector, said control sequence directing expression of said MOMP when introduced into a host to produce an immune response to said MOMP, and introducing said vector into a host.

In a further aspect of the present invention provides a method of producing a vaccine for protection of a host against disease caused by infection with a strain of Chlamydia, which comprises isolating a nucleotide sequence encoding a major outer membrane protein (MOMP) of a strain of Chlamydia or a MOMP fragment that generates a MOMP-specific immune response, operatively linking said nucleotide sequence to at least one control sequence to produce a non-replicating vector, the control sequence directing expression of said MOMP when introduced to a host to produce an immune response to said MOMP, and formulating said vector as a vaccine for in vivo administration to a host.

Advantages of the present invention, therefore, include a method of obtaining a protective immune response to infection carried by a strain of Chlamydia by DNA immunization of DNA encoding the major outer membrane protein of a-strain of Chlamydia.

Claim 1 of 9 Claims

What we claim is:

1. An immunogenic composition for in vivo administration to a host for the generation in the host of a protective immune response to a major outer membrane protein (MOMP) of a strain of Chiamydia, comprising:

a non-replicating plasmid vector comprising:

a nucleotide sequence encoding said MOMP or a fragment of said MOMP that generates a MOMP-specific immune response, and

a cptomeqalovirus promoter sequence operatively coupled to said nucleotide sequence for expression of said MOMP in the host; and

a pharmaceutically-acceptable carrier therefor.

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