Title:  Soluble herpesvirus glycoprotein complex vaccine

United States Patent:  6,156,319

Assignee:  The Trustees of the University of Pennsylvania (Philadelphia, PA)

Filed:  July 31, 1997

The invention is directed to a herpes simplex virus vaccine comprising a herpes simplex virus glycoprotein H-glycoprotein L complex. The invention is also directed to a vaccine comprising a DNA encoding a herpes simplex virus glycoprotein H-glycoprotein L complex. Also included is an antibody which specifically binds to a herpes simplex virus glycoprotein H-glycoprotein L complex and DNA encoding the same.

SUMMARY OF THE INVENTION

The invention relates to a vaccine comprising a soluble herpes simplex virus gHt-gL complex suspended in a pharmaceutically acceptable carrier.

In one aspect, the herpes simplex virus is selected from the group consisting of herpes simplex virus type 1 and herpes simplex virus type 2. Preferably, the herpes simplex virus is herpes simplex virus type 1.

In one embodiment, gHt is from a herpes simplex virus selected from herpes simplex virus type 1 and herpes simplex virus type 2.

In another embodiment, the gL is from a herpes simplex virus selected from herpes simplex virus type 1 and herpes simplex virus type 2.

In yet another embodiment, the gHt is from herpes simplex virus type 1 and comprises amino acid residues selected from the group consisting of 1-792, 1-648, 1-475, 1-324 and 1-275.

In a further embodiment, the gHt is herpes simplex virus type 1 gHt comprising amino acids 1-324.

In another embodiment, the gHt is herpes simplex virus type 1 gHt comprising amino acids 1-792 and the gL is herpes simplex virus type 1 gL comprising amino acids 1-168.

The vaccine of the invention may further include a substantially pure preparation of at least one of a herpes simplex virus gD, gB or gC.

Also included in the invention is a vaccine comprising an isolated DNA encoding a soluble herpes simplex virus gHt-gL complex suspended in a pharmaceutically acceptable carrier.

In one embodiment of this aspect of the invention, the vaccine includes an isolated DNA encoding at least one of a herpes simplex virus gD, gB or gC.

The invention also relates to a herpes simplex virus neutralizing antibody which specifically binds to a soluble herpes simplex virus gHt-gL complex.

The invention further relates to an isolated DNA encoding a herpes simplex virus neutralizing antibody which specifically binds to a soluble herpes simplex virus gHt-gL complex.

There is also included in the invention a method of immunizing a human patient against a herpes simplex virus infection comprising administering to the patient a vaccine comprising a soluble herpes simplex virus gHt-gL, complex suspended in a pharmaceutically acceptable carrier.

The invention further relates to a method of immunizing a human patient against a herpes simplex virus infection comprising administering to the patient a vaccine comprising an isolated DNA encoding a soluble herpes simplex virus gHt-gL complex suspended in a pharmaceutically acceptable carrier.

Also included in the invention is a method of treating a herpes simplex virus infection in a human patient comprising administering to the patient a vaccine comprising a soluble herpes simplex virus gHt-gL complex suspended in a pharmaceutically acceptable carrier.

The invention further includes a method of treating a herpes simplex virus infection in a human patient comprising administering to the patient a vaccine comprising an isolated DNA encoding a soluble herpes simplex virus gHt-gL complex suspended in a pharmaceutically acceptable carrier.

In each of the aforementioned methods of immunizing a human patient or of treating a herpes simplex virus infection in a human patient, the methods should be construed to optionally include the administration of a substantially pure preparation of at least one of a herpes simplex virus gD, gB or gC, or the administration of an isolated DNA encoding at least one of a herpes simplex virus gD, gB or gC.

There is further provided a method of treating a herpes simplex virus infection in a human patient comprising administering to the patient a herpes simplex virus neutralizing antibody which specifically binds to a soluble herpes simplex virus gHt-gL complex wherein the antibody is suspended in a pharmaceutically acceptable carrier.

Also included is a method of treating a herpes simplex virus infection in a human patient comprising administering to the patient an isolated DNA encoding a herpes simplex virus neutralizing antibody which specifically binds to a soluble herpes simplex virus gHt-gL complex, wherein the DNA is suspended in a pharmaceutically acceptable carrier.

In addition, the invention relates to a preparation of a soluble herpes simplex virus gHt-gL complex and a substantially pure preparation of a soluble herpes simplex virus gHt-gL complex.

In a preferred embodiment, the herpes simplex virus is selected from the group consisting of herpes simplex virus type 1 and herpes simplex virus type 2. Preferably, the herpes simplex virus is herpes simplex virus type 1.

In one aspect, the complex is suspended in a pharmaceutically acceptable carrier.

In another aspect, the gHt comprises amino acid residues selected from the group consisting of 1-792, 1-648, 1-475, 1-324 and 1-275.

In yet another aspect, the gHt comprises amino acids 1-324.

In another aspect, the gHt comprises amino acids 1-792 and the gL comprises amino acids 1-168.

The invention further relates to a cell, the DNA of the cell encoding a soluble herpes simplex virus gHt-gL complex.

In one aspect, the cell is HL-7.

There is also provided in the invention a method of modifying a cell to render it capable of secreting a soluble herpes simplex virus gf It-gL complex comprising introducing into the cell DNA encoding a truncated form of herpes simplex virus gH being gHt and full length herpes simplex virus gL, wherein the gHt and the gL are expressed in and secreted from the cell.

In one embodiment, the gHt comprises herpes simplex virus type 1 gH comprising amino acid residues selected from the group consisting of 1-792, 1-648, 1-475, 1-324 and 1-275.

The invention further relates to an isolated DNA comprising DNA encoding a herpes simplex virus gHt and a substantially full length herpes simplex virus gL.

Claim 1 of 14 Claims

What is claimed is:

1. A virus neutralizing effective amount of a soluble herpes simplex virus gHt-gL complex suspended in a pharmaceutically acceptable carrier.

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