Protective Humoral Immune Responses to the Human Immunodeficiency Virus Induced in Immunized Pigs: A Possible Source of Therapeutic Immunoglobulin Preparations

Abstract

The human immunodeficiency virus (HIV-1) induces progressive and fatal disease in infected hosts. Initially the human immune response appears to control HIV infection. This hypothesis is supported by the long latency period observed during HIV infection prior to development of the active disease state. Similarly the observation of fetal protection from HIV infection in some pregnant women who have high titered neutralizing antibody responses to the virus underscores the importance of the humoral response to HIV in limiting infection. Therefore antibody replacement therapy is likely to provide substantial clinical benefits in this and other infected populations. However, currently there is no safe source for human antibodies with the desired protective qualities necessary for passive immune therapies. For a passive immune therapy to be valid it must protect against a diverse collection of viral isolates. Such a task is likely to require a complex mixture of human antibodies or human substitute antibodies which are available in large quantities and target conserved regions of the viral envelope, such that protection from diverse isolates are realized. Porcine products have been used extensively in many human therapeutic replacement regimens. Their use is primarily due to genetic similarity of the two species at the amino acid level which results in a high acceptance of grafted prosthetics and excellent tolerance of repeatedly administered biologicals. Accordingly we have examined the immunoglobulin responses to the Human Immunodeficiency Virus (HIV-1) of the Yorkshire mixed breed pig. Immunized animals developed significant humoral immunity as judged by ELISA, Western blot, radioimmunoprecipitation, flow microfluorimetry as well as in functional assays including neutralization and syncytia inhibition. The high neutralizing activity obtained and the immunological similarity between human and porcine immunoglobulin suggests that further investigation into the use of porcine immunoglobulin as human replacement antibodies for the therapeutic treatment of HIV is warranted.