Biomedical subjects

Jay W Hooper

Publications and source records attributed to Jay W Hooper.

6 recordsLinked to original sources

PubMed2006

Subunit recombinant vaccine protects against monkeypox.

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.

Amino Acid Sequence↗

PubMed2005

Hantaan/Andes virus DNA vaccine elicits a broadly cross-reactive neutralizing antibody response in nonhuman primates.

At least four hantavirus species cause disease with prominent renal involvement-hemorrhagic fever with renal syndrome (HFRS); and several hantavirus strains cause disease with significant pulmonary involvement-hantavirus pulmonary syndrome (HPS). The most prevalent and lethal hantaviruses associated with HFRS and HPS are Hantaan virus (HTNV) and Andes virus (ANDV), respectively. Here, we constructed a DNA vaccine plasmid (pWRG/HA-M) that contains both the HTNV and ANDV M gene segments. Rhesus macaques vaccinated with pWRG/HA-M produced antibodies that bound the M gene products (i.e., G1 and G2 glycoproteins), and neutralized both HTNV and ANDV. Neutralizing antibody titers elicited by the dual-immunogen pWRG/HA-M, or single-immunogen plasmids expressing only the HTNV or ANDV glycoproteins, increased rapidly to high levels after a booster vaccination administered 1-2 years after the initial vaccination series. Memory responses elicited by this long-range boost exhibited an increased breadth of cross-neutralizing activity relative to the primary response. This is the first time that hantavirus M gene-based DNA vaccines have been shown to elicit a potent memory response, and to elicit antibody responses that neutralize viruses that cause both HFRS and HPS.

Animals↗

PubMed2005

Immunogenicity of combination DNA vaccines for Rift Valley fever virus, tick-borne encephalitis virus, Hantaan virus, and Crimean Congo hemorrhagic fever virus.

DNA vaccines for Rift Valley fever virus (RVFV), Crimean Congo hemorrhagic fever virus (CCHFV), tick-borne encephalitis virus (TBEV), and Hantaan virus (HTNV), were tested in mice alone or in various combinations. The bunyavirus vaccines (RVFV, CCHFV, and HTNV) expressed Gn and Gc genes, and the flavivirus vaccine (TBEV) expressed the preM and E genes. All vaccines were delivered by gene gun. The TBEV DNA vaccine and the RVFV DNA vaccine elicited similar levels of antibodies and protected mice from challenge when delivered alone or in combination with other DNAs. Although in general, the HTNV and CCHFV DNA vaccines were not very immunogenic in mice, there were no major differences in performance when given alone or in combination with the other vaccines.

Animals↗

PubMed2005

Smallpox vaccine-induced antibodies are necessary and sufficient for protection against monkeypox virus.

Vaccination with live vaccinia virus affords long-lasting protection against variola virus, the agent of smallpox. Its mode of protection in humans, however, has not been clearly defined. Here we report that vaccinia-specific B-cell responses are essential for protection of macaques from monkeypox virus, a variola virus ortholog. Antibody-mediated depletion of B cells, but not CD4+ or CD8+ T cells, abrogated vaccine-induced protection from a lethal intravenous challenge with monkeypox virus. In addition, passive transfer of human vaccinia-neutralizing antibodies protected nonimmunized macaques from severe disease. Thus, vaccines able to induce long-lasting protective antibody responses may constitute realistic alternatives to the currently available smallpox vaccine (Dryvax).

Animals↗

PubMed2003

Rescue of Hantaan virus minigenomes.

Hantavirus infections are a major public health concern worldwide. Their widespread geographical distribution and their ability to produce serious, often fatal, human disease underline the need for a system that allows manipulation of these viruses. We describe here the first successful establishment of a reverse genetics technology for Hantaan virus, the prototype of the genus Hantavirus. The system offers a unique opportunity to study the biology of hantaviruses, the pathogenesis of the diseases, and the efficacy of antiviral and prophylactic measures against hantavirus infections.

Animals↗

PubMed2003

The M2 gene segment is involved in the capacity of reovirus type 3Abney to induce the oily fur syndrome in neonatal mice, a S1 gene segment-associated phenotype.

Oral inoculation of reovirus type 3 Abney (T3A) into neonatal mice induces hepatitis and the biliary atresia-associated oily fur syndrome (OFS), a phenotype previously linked to the S1 gene. We found that following oral inoculation, none of three T3A mutants, JH2, JH3, and JH4, containing different single amino acid substitutions in the M2 gene, induced the OFS or extensive liver necrosis. Similarly, reassortant viruses containing both a JH4-S1 and a JH4-M2 gene segment did not induce the OFS, whereas another reassortant containing a JH4-S1 gene and a M2 gene from reovirus type 3 Dearing fully recovered this capacity. Together, these results constitute the first evidence for the involvement of the M2 gene in the S1 gene-associated capacity of T3A to induce hepatobiliary disease in neonatal mice.

Animals↗