Long‐term protection of macaques against high‐dose type D retrovirus challenge after immunization with recombinant vaccinia virus expressing envelope glycoproteins

ABSTRACT Recent events have raised concern over the use of pathogens, including variola virus, as biological weapons. Vaccination with Dryvax is associated with serious side effects and is contraindicated for many people, and the development of a safer effective smallpox vaccine is necessary. We evaluated an attenuated vaccinia virus, modified vaccinia virus Ankara (MVA), by use of a murine model to determine its efficacy against an intradermal (i.d.) or intranasal (i.n.) challenge with vaccinia virus (vSC8) or a recombinant vaccinia virus expressing murine interleukin-4 that exhibits enhanced virulence (vSC8-mIL4). After an i.d. challenge, 15 of 16 mice who were inoculated with phosphate-buffered saline developed lesions, one dose of intramuscularly administered MVA was partially protective (3 of 16 mice developed lesions), and the administration of two or three doses of MVA was completely protective (0 of 16 mice developed lesions). In unimmunized mice, an i.n. challenge with vSC8 caused a significant but self-limited illness, while vSC8-mIL4 resulted in lethal infections. Immunization with one or two doses of MVA prevented illness and reduced virus titers in mice who were challenged with either vSC8 or vSC8-mIL4. MVA induced a dose-related neutralizing antibody and vaccinia virus-specific CD8+-T-cell response. Mice immunized with MVA were fully protected from a low-dose vSC8-mIL4 challenge despite a depletion of CD4+ cells, CD8+ cells, or both T-cell subsets or an antibody deficiency. CD4+- or CD8+-T-cell depletion reduced the protection against a high-dose vSC8-mIL4 challenge, and the depletion of both T-cell subsets was associated with severe illness and higher vaccinia virus titers. Thus, MVA induces broad humoral and cellular immune responses that can independently protect against a molecularly modified lethal poxvirus challenge in mice. These data support the continued development of MVA as an alternative candidate vaccine for smallpox.

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Caprine arthritis-encephalitis lentivirus (CAEV) challenge of goats immunized with recombinant vaccinia virus expressing CAEV surface and transmembrane envelope glycoproteins

Veterinary Immunology and Immunopathology ◽

10.1016/0165-2427(94)90070-1 ◽

1994 ◽

Vol 42 (3-4) ◽

pp. 237-251 ◽

Cited By ~ 15

Author(s):

W.P. Cheevers ◽

D.P. Knowles ◽

T.C. McGuire ◽

T.V. Baszler ◽

G.A. Hullinger

Keyword(s):

Vaccinia Virus ◽

Recombinant Vaccinia Virus ◽

Envelope Glycoproteins ◽

Recombinant Vaccinia

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Long-Term Sterilizing Immunity to Rinderpest in Cattle Vaccinated with a Recombinant Vaccinia Virus Expressing High Levels of the Fusion and Hemagglutinin Glycoproteins

Journal of Virology ◽

10.1128/jvi.76.2.484-491.2002 ◽

2002 ◽

Vol 76 (2) ◽

pp. 484-491 ◽

Cited By ~ 25

Author(s):

Paulo H. Verardi ◽

Fatema H. Aziz ◽

Shabbir Ahmad ◽

Leslie A. Jones ◽

Berhanu Beyene ◽

...

Keyword(s):

Vaccinia Virus ◽

Lethal Dose ◽

Syncytium Formation ◽

Viral Disease ◽

Recombinant Vaccinia Virus ◽

Recombinant Vaccinia ◽

Heat Stable ◽

Infected Cells ◽

Sterilizing Immunity

ABSTRACT Rinderpest is an acute and highly contagious viral disease of ruminants, often resulting in greater than 90% mortality. We have constructed a recombinant vaccinia virus vaccine (v2RVFH) that expresses both the fusion (F) and hemagglutinin (H) genes of rinderpest virus (RPV) under strong synthetic vaccinia virus promoters. v2RVFH-infected cells express high levels of the F and H glycoproteins and show extensive syncytium formation. Cattle vaccinated intramuscularly with as little as 103 PFU of v2RVFH and challenged 1 month later with a lethal dose of RPV were completely protected from clinical disease; the 50% protective dose was determined to be 102 PFU. Animals vaccinated with v2RVFH did not develop pock lesions and did not transmit the recombinant vaccinia virus to contact animals. Intramuscular vaccination of cattle with 108 PFU of v2RVFH provided long-term sterilizing immunity against rinderpest. In addition to being highly safe and efficacious, v2RVFH is a heat-stable, inexpensive, and easily administered vaccine that allows the serological differentiation between vaccinated and naturally infected animals. Consequently, mass vaccination of cattle with v2RVFH could eradicate rinderpest.

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