Induction of immune responses to herpes simplex virus with liposomes containing viral antigens

Author

Paul Thomas Naylor

Date of Award

12-1981

Degree Type

Dissertation

Degree Name

Doctor of Philosophy

Major Professor

Leaf Huang

Committee Members

Richard Courtney, Jorge Churchich, Robert Bryant

Abstract

The immunogenicity of detergent extracted herpes simplex virus type I (HSV-I) antigens incorporated into liposomes were measured by their ability to induce in vitro secondary anti-HSV-l specific cytotoxic T lymphocyte (CTL) responses in splenocyte cultures from virus-primed mice or in vivo immune responses in mice.

First, in vitro secondary virus specific CTL responses could be induced provided the liposomes contained viral antigens along with plasma membrane antigens of the same H-2 haplotype as that of the virus primed responder cells. Responses did not occur in cultures stimulated with liposomes containing only viral antigens or with a mixture of liposomes composed respectively of lipid and viral antigens and those composed of lipid and plasma membrane antigens. Thus, it is essential that both the viral and H-2 antigens be incorporated into the same liposome for the induction process to occur.

The ability of these incorporated antigens to induce a CTL response was also dependent on the type of exogenous lipid used to make the liposomes. It was found that a phosphatidylcholine:cholesterol mixture, 7:2 mole ratio, gave the best response. It was also found that once either the viral glycoproteins on the H-2K^k antigen were purified and subsequently incorporated into liposomes with plasma membrane antigens or detergent extracted viral antigens respectively these liposome lost the ability ta induce a CTL response. The reason for this loss of induction capability is discussed in the ensuing chapters.

Secondly, liposome incorporated HSV-I antigens could induce on antibody response in mice whereas free .detergent extracted antigens could not. This in vivo response could be further enhanced by incorporating the B-cell adjuvant, lipid A into the same liposomes as the viral antigens. The induction was also found to be dependent on the dose of lipid A and HSV-1 antigens given. Although these liposomes induce a humoral response that is as good or better than that achieved by live virus they failed to induce any cellular responses.

Recommended Citation

Naylor, Paul Thomas, "Induction of immune responses to herpes simplex virus with liposomes containing viral antigens. " PhD diss., University of Tennessee, 1981.
https://trace.tennessee.edu/utk_graddiss/13488