Development of a safe live Leishmania vaccine line by gene replacement.

Vaccination with live Leishmania major has been shown to yield effective immunization in humans; however, this has been discontinued because of problems associated with virulence of the available vaccine lines. To circumvent this, we tested the ability of a dhfr-ts- null mutant of L. major, obtained by gene targeting, to infect and then to vaccinate mice against challenge with virulent L. major. Survival and replication of dhfr-ts- in macrophages in vitro were dependent upon thymidine, with parasites differentiating into amastigotes prior to destruction. dhfr-ts- parasites persisted in BALB/c mice for up to 2 months, declining with a half-life of 2-3 days. Nonetheless, dhfr-ts- was incapable of causing disease in both susceptible and immunodeficient (nu/nu) BALB/c mice. Animal infectivity could be partially restored by thymidine supplementation. When inoculated by the i.v., s.c., or i.m. routes into mice, dhfr-ts- could elicit substantial resistance to a subsequent challenge with virulent L. major. Thus, Leishmania bearing auxotrophic gene knockouts can be safe and induce protective immunity. Potentially, dhfr-ts- could be used as a platform for delivery of immunogens relevant to other diseases.

Severe Cutaneous Leishmaniasis in a Human Immunodeficiency Virus Patient Coinfected with Leishmania braziliensis and Its Endosymbiotic Virus.

Leishmaniaparasites cause a broad range of disease, with cutaneous afflictions being, by far, the most prevalent. Variations in disease severity and symptomatic spectrum are mostly associated to parasite species. One risk factor for the severity and emergence of leishmaniasis is immunosuppression, usually arising by coinfection of the patient with human immunodeficiency virus (HIV). Interestingly, several species ofLeishmaniahave been shown to bear an endogenous cytoplasmic dsRNA virus (LRV) of theTotiviridaefamily, and recently we correlated the presence of LRV1 withinLeishmaniaparasites to an exacerbation murine leishmaniasis and with an elevated frequency of drug treatment failures in humans. This raises the possibility of further exacerbation of leishmaniasis in the presence of both viruses, and here we report a case of cutaneous leishmaniasis caused byLeishmania braziliensisbearing LRV1 with aggressive pathogenesis in an HIV patient. LRV1 was isolated and partially sequenced from skin and nasal lesions. Genetic identity of both sequences reinforced the assumption that nasal parasites originate from primary skin lesions. Surprisingly, combined antiretroviral therapy did not impact the devolution ofLeishmaniainfection. TheLeishmaniainfection was successfully treated through administration of liposomal amphotericin B.

The correspondence of John Cleves Symmes : founder of the Miami Purchase, chiefly from the collection of Peter G. Thomson /

"Letters from Jonathan Dayton to John Cleves Symmes": p. 197-277.

The history of the state of Ohio,

Mode of access: Internet.

Easy entertainments for young people.

Mode of access: Internet.

Virginia's attitude toward slavery and secession /

Includes bibliographical references (p. 305-311).

The cathedral church of York; a description of its fabric and a brief history of the archi-episcopal see,

Mode of access: Internet.

A key to the disunion conspiracy. The partisan leader.

Original title: The partisan leader; a tale of the future. By Edward William Sidney [pseud.] ... Printed for the publishers by J. Caxton, 1856 [i.e. 1836]

Canada, and the Canada bill:

Mode of access: Internet.

The partisan leader.

Paged continuously; v.1: 1 p. 1., [v]-xv, 195 p.; v.2: [197]-392 p.

A carnival of sports, an entertainment representing such popular sports as tennis, archery, base-ball, boxing, football, etc. ...

Mode of access: Internet.

Map reading for aviators, with a chapter on aerial navigation,

Mode of access: Internet.

The partisan leader: a novel, and an apocalypse of the origin and struggles of the southern confederacy.

Secretly printed in 1836 with a fictitious imprint and date of 1856. cf. Allibone, Crit. dict. of Eng. lit.

Our English minsters,

Second series, "by the Very Rev. A. P. Purey-Cust and others."

A letter to His Royal Highness the Duke of Gloucester, Chancellor : on the present corrupt state of the University of Cambridge /

Mode of access: Internet.