Should remaining stockpiles of smallpox virus (variola) be destroyed?

In 2011, the World Health Organization will recommend the fate of existing smallpox stockpiles, but circumstances have changed since the complete destruction of these cultures was first proposed. Recent studies suggest that variola and its experimental surrogate, vaccinia, have a remarkable ability to modify the human immune response through complex mechanisms that scientists are only just beginning to unravel. Further study that might require intact virus is essential. Moreover, modern science now has the capability to recreate smallpox or a smallpox-like organism in the laboratory in addition to the risk of nature re-creating it as it did once before. These factors strongly suggest that relegating smallpox to the autoclave of extinction would be ill advised.

Significantly reduced CCR5-tropic HIV-1 replication in vitro in cells from subjects previously immunized with Vaccinia Virus.

BACKGROUND: At present, the relatively sudden appearance and explosive spread of HIV throughout Africa and around the world beginning in the 1950s has never been adequately explained. Theorizing that this phenomenon may be somehow related to the eradication of smallpox followed by the cessation of vaccinia immunization, we undertook a comparison of HIV-1 susceptibility in the peripheral blood mononuclear cells from subjects immunized with the vaccinia virus to those from vaccinia naive donors. RESULTS: Vaccinia immunization in the preceding 3-6 months resulted in an up to 5-fold reduction in CCR5-tropic but not in CXCR4-tropic HIV-1 replication in the cells from vaccinated subjects. The addition of autologous serum to the cell cultures resulted in enhanced R5 HIV-1 replication in the cells from unvaccinated, but not vaccinated subjects. There were no significant differences in the concentrations of MIP-1alpha, MIP-1beta and RANTES between the cell cultures derived from vaccinated and unvaccinated subjects when measured in culture medium on days 2 and 5 following R5 HIV-1 challenge. DISCUSSION: Since primary HIV-1 infections are caused almost exclusively by the CCR5-tropic HIV-1 strains, our results suggest that prior immunization with vaccinia virus might provide an individual with some degree of protection to subsequent HIV infection and/or progression. The duration of such protection remains to be determined. A differential elaboration of MIP-1alpha, MIP-1beta and RANTES between vaccinated and unvaccinated subjects, following infection, does not appear to be a mechanism in the noted protection.

Effective antiprotease-antibiotic treatment of experimental anthrax.

BACKGROUND: Inhalation anthrax is characterized by a systemic spread of the challenge agent, Bacillus anthracis. It causes severe damage, including multiple hemorrhagic lesions, to host tissues and organs. It is widely believed that anthrax lethal toxin secreted by proliferating bacteria is a major cause of death, however, the pathology of intoxication in experimental animals is drastically different from that found during the infectious process. In order to close a gap between our understanding of anthrax molecular pathology and the most prominent clinical features of the infectious process we undertook bioinformatic and experimental analyses of potential proteolytic virulence factors of B. anthracis distinct from lethal toxin. METHODS: Secreted proteins (other than lethal and edema toxins) produced by B. anthracis were tested for tissue-damaging activity and toxicity in mice. Chemical protease inhibitors and rabbit immune sera raised against B. anthracis proteases were used to treat mice challenged with B. anthracis (Sterne) spores. RESULTS: B. anthracis strain delta Ames (pXO1-, pXO2-) producing no lethal and edema toxins secrets a number of metalloprotease virulence factors upon cultivation under aerobic conditions, including those with hemorrhagic, caseinolytic and collagenolytic activities, belonging to M4 and M9 thermolysin and bacterial collagenase families, respectively. These factors are directly toxic to DBA/2 mice upon intratracheal administration at 0.5 mg/kg and higher doses. Chemical protease inhibitors (phosphoramidon and 1, 10-phenanthroline), as well as immune sera against M4 and M9 proteases of B. anthracis, were used to treat mice challenged with B. anthracis (Sterne) spores. These substances demonstrate a substantial protective efficacy in combination with ciprofloxacin therapy initiated as late as 48 h post spore challenge, compared to the antibiotic alone. CONCLUSION: Secreted proteolytic enzymes are important pathogenic factors of B. anthrasis, which can be considered as effective therapeutic targets in the development of anthrax treatment and prophylactic approaches complementing anti-lethal toxin therapy.