ABSTRACT
We utilized SIV(mne) infection of Macaca fascicularis to assess the efficacy of DNA vaccination alone, and as a priming agent in combination with subunit protein boosts. All SIV(mne) structural and regulatory genes were expressed using the human cytomegalovirus Immediate Early-1 promoter in plasmids that directed the formation of virus-like particles in vitro. Macaques (n = 4) were immunized intradermally and intramuscularly four times over 36 weeks with 3 mg plasmid DNA. A second group (n = 4) received two DNA priming inoculations followed by two intramuscular boosts consisting of 250 microg recombinant Env gp160 and 250 microg recombinant Gag-Pol particles in MF-59 adjuvant. These regimens elicited modest cellular immunity prior to challenge. Humoral immune responses to Env gp160 were elicited and sustained by both vaccine protocols, and as expected antibody titers were higher in the protein subunit-boosted animals. Neutralizing antibodies prior to challenge were measurable in two of four subunit-boosted macaques. The two vaccine regimens elicited comparable helper T cell responses at the time of challenge. Vaccinees and mock-immunized controls (n = 4) were challenged intrarectally at week 38 with uncloned SIV(mne). Following challenge all macaques became infected, but both vaccine regimens resulted in reduced peak virus loads (p = 0.07) and significantly improved maintenance of peripheral CD4(+) T cell counts postchallenge (p = 0.007, DNA alone and p = 0.01, all vaccinees). There was no significant difference between the two vaccine groups in levels of plasma viremia or maintenance of CD4(+) T cell counts postchallenge.
Subject(s)
SAIDS Vaccines/immunology , Simian Acquired Immunodeficiency Syndrome/immunology , Simian Immunodeficiency Virus/immunology , Vaccines, DNA/immunology , Animals , Antibodies, Viral/blood , Antigens, Viral/immunology , CD4 Lymphocyte Count , Fusion Proteins, gag-pol/genetics , Fusion Proteins, gag-pol/immunology , Gene Products, env/immunology , HIV Envelope Protein gp160/genetics , HIV Envelope Protein gp160/immunology , Immunity, Cellular , Macaca fascicularis , Neutralization Tests , Plasmids , Proviruses/genetics , Proviruses/isolation & purification , RNA, Viral/blood , SAIDS Vaccines/administration & dosage , Simian Acquired Immunodeficiency Syndrome/prevention & control , Simian Acquired Immunodeficiency Syndrome/virology , Vaccines, DNA/administration & dosage , Vaccines, Subunit/administration & dosage , Vaccines, Subunit/immunology , Viral LoadABSTRACT
End-stage renal failure is often considered a relative contraindication for total artificial heart implantation due to the increased risk of mortality after transplantation. We report the successful treatment of a patient having heart and renal failure with the CardioWest (SynCardia Inc, Tucson, AZ) total artificial heart for bridge-to-cardiac transplantation of a heart and kidney.
Subject(s)
Heart Failure/surgery , Heart Transplantation/methods , Heart, Artificial , Kidney Failure, Chronic/surgery , Kidney Transplantation/methods , Follow-Up Studies , Heart Failure/complications , Humans , Kidney Failure, Chronic/complications , Male , Middle Aged , Prosthesis DesignABSTRACT
We assessed four prime-boost vaccine regimens with a Gene Gun component for SHIV89.6P in Macaca nemestrina. A dosing experiment using beta-galactosidase plasmid showed that 30 or 45 shots per dose elicited higher titer antibody than smaller doses. For SHIV89.6P, we administered a six-plasmid vaccine capable of producing non-infectious virions in vivo in combination with either vaccinia recombinants or inactivated virus. DNA prime/vaccinia boost, or the reverse, elicited strong immune responses. The SHIV89.6P challenge virus was grown in M. nemestrina peripheral blood mononuclear cells and titered in vivo intrarectally. As has been observed for SHIV89.6P in M. mulatta, the infected M. nemestrina experienced rapid and severe loss of circulating CD4+ T cells. Vaccinated macaques were challenged three weeks after the last boost. DNA prime/vaccina boost or vaccina prime/DNA boost protected 11/12 animals from acute CD4+ T cell depletion and disease, while other regimens were not effective.