Subunit recombinant vaccine protects against monkeypox.

Abstract

The smallpox vaccine Dryvax, a live vaccinia virus (VACV), protects against smallpox and monkeypox, but is contraindicated in immunocompromised individuals. Because Abs to VACV mediate protection, a live virus vaccine could be substituted by a safe subunit protein-based vaccine able to induce a protective Ab response. We immunized rhesus macaques with plasmid DNA encoding the monkeypox orthologs of the VACV L1R, A27L, A33R, and B5R proteins by the intradermal and i.m. routes, either alone or in combination with the equivalent recombinant proteins produced in Escherichia coli. Animals that received only DNA failed to produce high titer Abs, developed innumerable skin lesions after challenge, and died in a manner similar to placebo controls. By contrast, the animals vaccinated with proteins developed moderate to severe disease (20-155 skin lesions) but survived. Importantly, those immunized with DNA and boosted with proteins had mild disease with 15 or fewer lesions that resolved within days. DNA/protein immunization elicited Th responses and binding Ab titers to all four proteins that correlated negatively with the total lesion number. The sera of the immunized macaques recognized a limited number of linear B cell epitopes that are highly conserved among orthopoxviruses. Their identification may guide future efforts to develop simpler, safer, and more effective vaccines for monkeypox and smallpox.

• Authors: Jean-Michel Heraud, Yvette Edghill-Smith, Victor Ayala, Irene Kalisz, Janie Parrino, Vaniambadi S Kalyanaraman, Jody Manischewitz, Lisa R King, Anna Hryniewicz, Christopher J Trindade, Meredith Hassett, Wen-Po Tsai, David Venzon, Aysegul Nalca, Monica Vaccari, Peter Silvera, Mike Bray, Barney S Graham, Hana Golding, Jay W Hooper, Genoveffa Franchini
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 177 Issue 4 Pg. 2552-64 (Aug 15 2006) ISSN: 0022-1767 [Print] United States
• PMID: 16888017 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural)

Chemical References

• Antibodies, Viral
• Antigens, Viral
• DNA, Viral
• DryVax vaccine
• Smallpox Vaccine
• Vaccines, Subunit
• Vaccines, Synthetic
• Viral Vaccines

Topics

• Amino Acid Sequence
• Animals
• Antibodies, Viral (biosynthesis, blood)
• Antigens, Viral (administration & dosage, genetics, immunology)
• DNA, Viral (administration & dosage, immunology)
• Disease Models, Animal
• Macaca mulatta
• Molecular Sequence Data
• Monkeypox (immunology, prevention & control)
• Monkeypox virus (genetics, immunology)
• Smallpox Vaccine (adverse effects, immunology)
• Vaccines, Subunit (administration & dosage, genetics, immunology)
• Vaccines, Synthetic (administration & dosage, genetics, immunology)
• Viral Vaccines (administration & dosage, genetics, immunology)