Correlates of GLA family adjuvants' activities.

Lipopolysaccharide (LPS) is a well-defined agonist of Toll-like receptor (TLR) 4 that activates innate immune responses and influences the development of the adaptive response during infection with Gram-negative bacteria. Many years ago, Dr. Edgar Ribi separated the adjuvant activity of LPS from its toxic effects, an effort that led to the development of monophosphoryl lipid A (MPL). MPL, derived from Salmonella minnesota R595, has progressed through clinical development and is now used in various product-enabling formulations to support the generation of antigen-specific responses in several commercial and preclinical vaccines. We have generated several synthetic lipid A molecules, foremost glucopyranosyl lipid adjuvant (GLA) and second-generation lipid adjuvant (SLA), and have advanced these to clinical trial for various indications. In this review we summarize the potential and current positioning of TLR4-based adjuvant formulations in approved and emerging vaccines.

Updates on the use of vaccines in dermatological conditions.

Numerous vaccines are being actively developed for use in dermatologic diseases. Advances in the fields of immunotherapy, genetics and molecular medicine have allowed for the design of prophylactic and therapeutic vaccines with immense potential in managing infections and malignancies of the skin. This review addresses the different vaccines available for use in dermatological diseases and those under development for future potential use. The major limitation of our review is its complete reliance on published data. Our review is strictly limited to the availability of published research online through available databases. We do not cite any of the authors' previous publications nor have we conducted previous original research studies regarding vaccines in dermatology. Strength would have been added to our paper had we conducted original studies by our research team regarding the candidate vaccines delineated in the paper.

Large unilamellar vesicles as trehalose-stabilised vehicles forvaccines storage time and in vivo studies

Liposomes, as a pharmaceutical formulation must display a long shelf life. The recombinant heat-shock protein fromMycobacterium leprae (18-kDa hsp) or its N-acylated derivative, when entrapped within or externally associated with largeunilamellar vesicles, acts as a T-epitope source. Freeze-fracture electron microscopy shows unequivocally that trehaloseavoids aggregation and fusion of these vesicles. Formulations containing trehalose retained up to 98% of the entrappedprotein. The highest antibody level is obtained with formulations containing trehalose. The adjuvant effect depends on theliposomal membrane integrity.

Vacunas para la lepra / Vaccines for leprosy

La lepra, enfermedad de Hansen o hanseniasis, es una enfermedad infecciosa crónica del hombre causada por Mycobacterium leprae; afecta a los nervios periféricos, la piel y la mucosa de las vías respiratorias superiores y secundariamente a ojos, huesos, músculos y testículos. La premisa mayor para el control de la lepra a través de la vacunación se puede enunciar de la manera siguiente: la inducción de reactividad inmunológica celular contra antígenos de M. leprae , tendrá como consecuencia que queden protegidos en contra de la infección. Esta supuesta correlación entre la respuesta inmunológica celular y la protección está basada en el espectro clínico de la enfermedad. La premisa menor relacionada al control de la lepra por medio de vacunas está basada en hallazgos experimentales: tanto M. leprae como algunas microbacterias cultivables pueden inducir reactividad inmunológica celular a los antígenos de M. leprae. Actualmente se le han dado dos usos racionales a las vacunas experimentales contra la lepra: uno es la inmunoterapia con el propósito de que en los pacientes inmunológicamente anérgicos a M. leprae, se logre despertar una respuesta inmunológica celular y así eliminen su infección; el otro empleo es en la inmunoprofilaxis, a fin de proteger a una población en riesgo de adquirir la infección o la enfermedad. Hasta ahora no se ha obtenido ninguna vacuna contra la lepra, hay varios candidatos en el desarrollo y por ello será más adecuado llamarles "candidatos a vacuna" más que "la vacuna de...."

Immunotherapy with a mixture of Mycobacterium leprae and BCG in different forms of leprosy and in Mitsuda-negative contacts.

A total of 529 weak or non-reactors to M. leprae, including Mitsuda-negative contacts and patients with leprosy, were vaccinated once or repeatedly, as necessary, with a mixture of 6 x 10(8) purified, heat-killed M. leprae and 0.01 mg to 0.2 mg of viable BCG. Clinical, histopathological and immunological criteria were used to evaluate the response of these individuals. Clinical changes, including sharper definition of borders and progressive flattening and regression of lesions, were observed in 57% of the active LL cases and 76% of the active BL cases. Histopathological study revealed infiltration of the lesions by mononuclear cells, appearance of epithelioid differentiation, and fragmentation of the microorganisms. Delayed-type skin tests with soluble antigen from purified M. leprae became positive in significant numbers of each group studied. These results demonstrate the efficacy of combined immunotherapy in low-resistance forms of leprosy and potential utility in the immunoprophylaxis of the disease.

Lack of a sustained protection against murine leprosy in C3H mice vaccinated with extracts of Mycobacterium lepraemurium in admixture with Mycobacterium bovis (BCG).

Inbred C3H mice were vaccinated intradermally with a single dose of live BCG, whole extracts of mechanically disrupted Mycobacterium lepraemurium (MLM), or a mixture of both these agents. Four weeks later, they were infected in one hind foot pad with freshly harvested MLM. Vaccination with BCG-containing preparations significantly reduced the multiplication of MLM in the infected foot pad and the bacillary dissemination to the draining popliteal lymph node and the spleen, while vaccination with MLM extracts solely limited the growth of MLM in the foot pad. MLM antigens in admixture with BCG did not offer a better protection than BCG alone. The protective effect was observed near the 15th week after the infection. At 30 weeks post-infection, no significant difference in bacillary counts was noted between the vaccinated and unvaccinated mice. In addition, the mean survival time of vaccinated mice did not significantly differ from that of control mice. Thus, in the C3H mouse, vaccination was able to limit temporarily the growth and dissemination of MLM, but these effects were unable to stop the fatal progression of murine leprosy.