Cynomolgus macaques were exposed to the Angola strain of Lake Victoria Marburg virus (MARV) by aerosol to examine disease course and lethality. Macaques became febrile 4 to 7 days postexposure; the peak febrile response was delayed 1 to 2 days in animals that received a lower dose; viremia coincided with the onset of fever. All 6 macaques succumbed to the infection, with the 3 macaques in the low-dose group becoming moribund on day 9, a day later than the macaques in the high-dose group. Gross pathologic lesions included maculopapular cutaneous rash; pulmonary congestion and edema; pericardial effusion; enlarged, congested, and/or hemorrhagic lymphoid tissues; enlarged friable fatty liver; and pyloric and duodenal congestion and/or hemorrhage. Fibrinous interstitial pneumonia was the most consistent pulmonary change. Lymphocytolysis and lymphoid depletion, as confirmed by TUNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling), were observed in the mediastinal lymph nodes and spleen. MARV antigen was detected in the lungs, mediastinal lymph nodes, spleen, and liver of all animals examined. In infected macaques, nuclear expression of interleukin-33 was lost in pulmonary arteriolar and mediastinal lymph node high endothelial venule endothelial cells; interleukin-33-positive fibroblastic reticular cells in the mediastinal lymph node were consistently negative for MARV antigen. These macaques exhibited a number of features similar to those of human filovirus infections; as such, this model of aerosolized MARV-Angola might be useful in developing medical countermeasures under the Animal Rule.

A Yersinia pestis-derived fusion protein (F1-V) has shown great promise as a protective antigen against aerosol challenge with Y. pestis in murine studies. In the current study, we examined different prime-boost regimens with F1-V and demonstrate that (i) boosting by a route other than the route used for the priming dose (heterologous boosting) protects mice as well as homologous boosting against aerosol challenge with Y. pestis, (ii) parenteral immunization is not required to protect mice against aerosolized plague challenge, (iii) the route of immunization and choice of adjuvant influence the magnitude of the antibody response as well as the immunoglobulin G1 (IgG1)/IgG2a ratio, and (iv) inclusion of an appropriate adjuvant is critical for nonparenteral immunization.Recently, a great deal of attention has been directed towards needle-free immunization strategies as alternative methods for vaccine delivery. Both mucosal (intranasal [i.n.], oral, and rectal) and transcutaneous (t.c.) immunization in the presence of an appropriate adjuvant have been shown to induce humoral and cellular immune responses in both the systemic and mucosal compartments of immunized animals. Alternating routes for delivery of the priming dose and booster dose in immunizations, so-called prime-boost strategies, have also been examined. Such prime-boost strategies could be particularly important in an imminent or postrelease bioterrorism event if it is possible to administer a parenteral priming dose and, at the same time, distribute a follow-up patch, pill, or nasal applicator that could be self administered. Such vaccine strategies would greatly improve national preparedness.In a recent study, we evaluated different prime-boost regimens, including parenteral, mucosal, and transcutaneous delivery, in order to explore the effect of changing the route of prime and boost on the ability of the recombinant Yersinia pestis-derived fusion protein (F1-V) to promote the development of long-lasting, high-titer antibodies (13). F1-V has been shown to provide protection against flea-borne, subcutaneous (s.c.), and aerosol challenge and has the potential to provide protective immunity against pneumonic as well as bubonic plague due to either wild-type F1 ϩ Y. pestis or to naturally occurring F1 Ϫ variants (16, 17). The most significant finding of our previous study is that boosting by a different (heterologous) route than the priming dose can be as effective as or more effective than homologous boosting for induction of either serum or bronchoalveolar anti-F1-V immunoglobulin G1 (IgG1) responses.In the current study, we examined the abilities of different prime-boost regimens with recombinant F1-V to protect mice against aerosol challenge with Y. pestis. We also examined the role of the coadministered adjuvant in inducing protection. For parenteral immunization, mice were immunized s.c. with 10 g of F1-V alone or adsorbed to alum adjuvant (2.0% Alhydrogel, batch no. 3275; Superfos Biosector, Vedbaek, Denmark) brought to a final volume of 100 l with ...

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Tularemia is a zoonotic disease caused by Francisella tularensis, which is transmitted to humans most commonly by contact with infected animals, tick bites, or inhalation of aerosolized bacteria. F. tularensis is highly infectious via the aerosol route; inhalation of as few as 10-50 organisms can cause pneumonic tularemia. Left untreated, the pneumonic form has more than > 30% case-fatality rate but with early antibiotic intervention can be reduced to 3%. This study compared tularemia disease progression across three species of nonhuman primates [African green monkey (AGM), cynomolgus macaque (CM), and rhesus macaque (RM)] following aerosolized F. tularensis Schu S4 exposure. Groups of the animals exposed to various challenge doses were observed for clinical signs of infection and blood samples were analyzed to characterize the disease pathogenesis. Whereas the AGMs and CMs succumbed to disease following challenge doses of 40 and 32 colony forming units (CFU), respectively, the RM lethal dose was 276,667 CFU. Following all challenge doses that caused disease, the NHPs experienced weight loss, bacteremia, fever as early as 4 days post exposure, and tissue burden. Necrotizing-to-pyogranulomatous lesions were observed most commonly in the lung, lymph nodes, spleen, and bone marrow. Overall, the CM model consistently manifested pathological responses similar to those resulting from inhalation of F. tularensis in humans and thereby most closely emulates human tularemia disease. The RM model displayed a higher tolerance to infection and survived exposures of up to 15,593 CFU of aerosolized F. tularensis.

From space weapons to mind reading, the books on this year's list tell tales of scientific transformation, balancing historical insights with urgent calls to action. Consider a transgender scientist's reflections on his legacy or tag along on a quest to save a tiny porpoise from extinction. Crack open a history of immunology or confront the future of artificial intelligence. Why would 12 men dine on purposely poisoned foods? Can we overcome "chronophobia"? What can termites teach us about technology? Read on to discover these answers and more. — Valerie Thompson

Historical Landmarks1346 Mongols catapult plague-infected corpses over the walls into Kaffa , with the intent of causing a plague epidemic upon the Genoan enemy (Derbes, 1966).1767 During the French and Indian War, British forces in North America give blankets used by smallpox patients to the Native Americans (Christopher et al., 1997).1917 Germans use anthrax and glanders (Burkholderia mallei) to infect livestock and animal feed for export to the Allied Forces (Christopher et al., 1997).1937 Japan creates "Unit 731," a BW (Biowarfare) research facility in Manchuria, where experimental infections were carried out on Chinese prisoners. More than 10,000 people die after exposure to plague, anthrax, tularemia, syphilis, and other agents. It is believed that the facility also had millions of rats infected with fleas carrying Yersinia pestis (Girdwood, 1985;Harris, 1992).1939 Japan poisons Soviet water supply with intestinal pathogens at Mongolian border (Nomonhan incident) (Williams and Wallace, 1989).1940 Japan drops rice and wheat mixed with plague-carrying fleas over China and Manchuria (Williams and Wallace, 1989).1942 The U.S. begins biological weapons program and chooses Camp Detrick, Frederick, Maryland, as its research and development site.Research efforts initially concentrated on the use of anthrax and botulinum toxin as bioweapons (Christopher et al., 1997).1943 England tests anthrax bombs to kill sheep on Gruinard Island ("Anthrax Island") off the coast of Scotland. Viable anthrax spores were still found on the island 40 years later (Manchee et al., 1982).1979 Outbreak of pulmonary anthrax in Sverdlovsk, U.S.S.R. caused by an accidental release of anthrax spores from a Soviet military microbiological facility. Hundreds are exposed and at least 67 die (Meselson et al., 1994).1984 Outbreak of salmonellosis in Oregon, U.S., after members of the Rajneesh cult intentionally contaminate salad bars with Salmonella typhimurium (Torok et al., 1997).1985 Iraq develops biological weapons including anthrax, botulinum toxin, and aflatoxin (Christopher et al., 1997).1993 Members of the Japanese cult of Aum Shinrikyo attempt an aerosolized release of anthrax from the tops of buildings in Tokyo (Smithson, 2000).1996 Outbreak of Shigella dysenteriae in Texas, U.S. after workers ingest food that was intentionally contaminated with this bacteria (Kolavic et al., 1997).