Retroviruses, long associated with leukemia and sarcoma of animals, have recently been implicated as the etiological agents of human T cell leukemia and human acquired immune deficiency syndrome (AIDS). The identification of these agents makes it possible to consider various ways of prevention. The most promising approach is development of a vaccine that could be administered to individuals at risk. The vaccinia vector system has been shown to produce both humoral and cell mediated immunity against a variety of infectious agents. Since human retroviruses have not yet been shown to produce disease in animals, initial vaccine work must be done with animal retroviruses. Friend leukemia virus complex is a useful model system since it produces an acute disease in adult mice which can be prevented by repeated immunization with the envelope glycoprotein. The envelope gene of Friend murine leukemia virus (MuLV) was inserted into vaccinia virus under the control of a vaccinia virus promoter that is active at early and late times after infection. Pulse-labeling experiments indicated that an MuLV polypeptide of 85 kD was synthesized and subsequently processed to polypeptides of 70 kD and 15 kD. Immunofluorescence studies indicated that the 70 kD polypeptide was inserted into the cell membrane. Mice vaccinated with the recombinant virus produced antibodies to the MuLV envelope protein and were protected against the development of splenomegaly upon intravenous challenge with MuLV. A similar procedure was used to prepare vaccinia virus recombinants that express the envelope gene of HTLV-III, the causative agent of AIDS. Immunoblotting and immunoprecipitation studies indicated that the 160 kD polypeptide is synthesized and processed correctly. The ability of this recombinant to induce an immune response in experimental animals is under investigation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000416-02
Application #
4688531
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Niaid Extramural Activities
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Cox, Josephine H; Ferrari, Maria G; Earl, Patricia et al. (2012) Inclusion of a CRF01_AE HIV envelope protein boost with a DNA/MVA prime-boost vaccine: Impact on humoral and cellular immunogenicity and viral load reduction after SHIV-E challenge. Vaccine 30:1830-40
Wyatt, Linda S; Earl, Patricia L; Xiao, Wei et al. (2009) Elucidating and minimizing the loss by recombinant vaccinia virus of human immunodeficiency virus gene expression resulting from spontaneous mutations and positive selection. J Virol 83:7176-84
Wyatt, Linda S; Belyakov, Igor M; Earl, Patricia L et al. (2008) Enhanced cell surface expression, immunogenicity and genetic stability resulting from a spontaneous truncation of HIV Env expressed by a recombinant MVA. Virology 372:260-72
Wyatt, Linda S; Earl, Patricia L; Vogt, Jennifer et al. (2008) Correlation of immunogenicities and in vitro expression levels of recombinant modified vaccinia virus Ankara HIV vaccines. Vaccine 26:486-93
Lai, Lilin; Vodros, Dalma; Kozlowski, Pamela A et al. (2007) GM-CSF DNA: an adjuvant for higher avidity IgG, rectal IgA, and increased protection against the acute phase of a SHIV-89.6P challenge by a DNA/MVA immunodeficiency virus vaccine. Virology 369:153-67
Robinson, Harriet L; Sharma, Sunita; Zhao, Jun et al. (2007) Immunogenicity in macaques of the clinical product for a clade B DNA/MVA HIV vaccine: elicitation of IFN-gamma, IL-2, and TNF-alpha coproducing CD4 and CD8 T cells. AIDS Res Hum Retroviruses 23:1555-62
Liu, Jinyan; Hellerstein, Michael; McDonnel, Michael et al. (2007) Dose-response studies for the elicitation of CD8 T cells by a DNA vaccine, used alone or as the prime for a modified vaccinia Ankara boost. Vaccine 25:2951-8
Kwissa, Marcin; Amara, Rama R; Robinson, Harriet L et al. (2007) Adjuvanting a DNA vaccine with a TLR9 ligand plus Flt3 ligand results in enhanced cellular immunity against the simian immunodeficiency virus. J Exp Med 204:2733-46
Earl, Patricia L; Americo, Jeffrey L; Wyatt, Linda S et al. (2007) Recombinant modified vaccinia virus Ankara provides durable protection against disease caused by an immunodeficiency virus as well as long-term immunity to an orthopoxvirus in a non-human primate. Virology 366:84-97
Brave, Andreas; Boberg, Andreas; Gudmundsdotter, Lindvi et al. (2007) A new multi-clade DNA prime/recombinant MVA boost vaccine induces broad and high levels of HIV-1-specific CD8(+) T-cell and humoral responses in mice. Mol Ther 15:1724-33

Showing the most recent 10 out of 60 publications