Harnessing Innate Immunity to Treat Infections: Heat-Killed as a Novel Biotherapeutic.

Tuberculosis, caused by (), is a serious and devastating infectious disease worldwide. Approximately a quarter of the world population harbors latent infection without pathological consequences. Exposure of immunocompetent healthy individuals with does not result in active disease in more than 90% individuals, suggesting a defining role of host immunity to prevent and/or clear early infection.

Heterologous Immunity between Adenoviruses and Hepatitis C Virus (HCV): Recombinant Adenovirus Vaccine Vectors Containing Antigens from Unrelated Pathogens Induce Cross-Reactive Immunity Against HCV Antigens.

Host immune responses play an important role in the outcome of infection with hepatitis C virus (HCV). They can lead to viral clearance and a positive outcome, or progression and severity of chronic disease. Extensive research in the past >25 years into understanding the immune responses against HCV have still resulted in many unanswered questions implicating a role for unknown factors and events.

Future Path Toward TB Vaccine Development: Boosting BCG or Re-educating by a New Subunit Vaccine.

Tuberculosis (TB), an infectious disease caused by (), kills 5,000 people per day globally. Rapid development and spread of various multi drug-resistant strains of emphasize that an effective vaccine is still the most cost-effectives and efficient way of controlling and eradicating TB. Bacillus Calmette-Guerin (BCG), the only licensed TB vaccine, still remains the most widely administered human vaccine, but is inefficient in protecting from pulmonary TB in adults.

Unsolved Puzzles Surrounding HCV Immunity: Heterologous Immunity Adds Another Dimension.

Chronic infection with hepatitis C virus (HCV) afflicts 3% of the world's population and can lead to serious and late-stage liver diseases. Developing a vaccine for HCV is challenging because the correlates of protection are uncertain and traditional vaccine approaches do not work. Studies of natural immunity to HCV in humans have resulted in many enigmas.

Novel lipopeptides of ESAT-6 induce strong protective immunity against Mycobacterium tuberculosis: Routes of immunization and TLR agonists critically impact vaccine's efficacy.

Mycobacterium tuberculosis (Mtb), the bacterial cause of tuberculosis, is a leading infectious agent worldwide. The development of a new vaccine against Mtb is essential to control global spread of tuberculosis, since the current vaccine BCG is not very effective and antibiotic resistance is a serious, burgeoning problem. ESAT-6 is a secreted protein of Mtb, which is absent in BCG but has been implicated in inducing protective immunity against Mtb.

Heterologous Immunity between Adenoviruses and Hepatitis C Virus: A New Paradigm in HCV Immunity and Vaccines.

Adenoviruses (Ad) are commonly used as vectors for gene therapy and/or vaccine delivery. Recombinant Ad vectors are being tested as vaccines for many pathogens. We have made a surprising observation that peptides derived from various hepatitis C virus (HCV) antigens contain extensive regions of homology with multiple adenovirus proteins, and conclusively demonstrate that adenovirus vector can induce robust, heterologous cellular and humoral immune responses against multiple HCV antigens.

Immunization with Recombinant Adenoviral Vectors Expressing HCV Core or F Proteins Leads to T Cells with Reduced Effector Molecules Granzyme B and IFN-γ: A Potential New Strategy for Immune Evasion in HCV Infection.

Multispecific, broad, and potent T cell responses have been correlated with viral clearance in hepatitis C virus (HCV) infection. However, the majority of infected patients develop chronic infection, suggesting that natural infection mostly leads to development of inefficient T cell immunity. Multiple mechanisms of immune modulation and evasion have been shown in HCV infection through various investigations.

Recombinant adenoviral vector expressing HCV NS4 induces protective immune responses in a mouse model of Vaccinia-HCV virus infection: a dose and route conundrum.

Hepatitis C virus (HCV) leads to chronic infection in the majority of infected patients presumably due to failure or inefficiency of the immune responses generated. Both antibody and cellular immune responses have been suggested to be important in viral clearance. Non-replicative adenoviral vectors expressing antigens of interest are considered as attractive vaccine vectors for a number of pathogens.

4'-Substituted pyrimidine nucleosides lacking 5'-hydroxyl function as potential anti-HCV agents.

Hepatitis C virus (HCV) infection is one of the major health problems worldwide. If left untreated, it leads to liver cirrhosis, liver cancer and death. Herein, we report synthesis and anti-HCV activity of a new class of pyrimidine nucleosides possessing a 4'-carboxymethyl (9-16, 21 and 23) or 4'-carboxamide function (17-19 and 24).

A new class of pyrimidine nucleosides: inhibitors of hepatitis B and C viruses.

Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are major health threats worldwide leading to liver cirrhosis, liver cancer and mortality. Herein, we report a new category of dideoxy pyrimidine nucleosides possessing a 4'-carboxyl (or carboxymethyl) function (7-9, 13, 16, 17), which are discovered as potential antiviral agents. For the first time, these nucleosides are recognized to be inhibitors of HBV and/or HCV replication.

Improvement in the antifilarial efficacy of doxycycline and rifampicin by combination therapy and drug delivery approach.

The present investigation deals with the evaluation of antifilarial efficacy of liposome entrapped antiwolbachial antibiotics doxycycline and rifampicin (5 doses at 10 mg/kg, subcutaneously for 15 days) alone and/or in combination with standard filaricide diethylcarbamazine (DEC) against human lymphatic filariid Brugia malayi in rodent host Mastomys coucha. The delivery system maintained the sustained release of antibiotics up to 48 h and significantly (P < 0.05) augmented the antifilarial potential of these antibiotics over their free administration.

Bacterially expressed recombinant envelope protein domain III of Japanese encephalitis virus (rJEV-DIII) elicits Th1 type of immune response in BALB/c mice.

Japanese encephalitis is a major cause of encephalitis in Asia. Cases occur largely in rural areas of the South and East Asian region resulting in significant morbidity and mortality. Multiple vaccines exist to control Japanese encephalitis, but all suffer from problems.

Tetracycline treatment targeting Wolbachia affects expression of an array of proteins in Brugia malayi parasite.

Wolbachia is an intracellular endosymbiont of Brugia malayi parasite whose presence is essential for the survival of the parasite. Treatment of B. malayi-infected jirds with tetracycline eliminates Wolbachia, which affects parasite survival and fitness.

Adjuvanticity and protective immunity of Plasmodium yoelii nigeriensis blood-stage soluble antigens encapsulated in fusogenic liposome.

In our previous studies we established fusogenic properties of lipids isolated from edible yeast Saccharomyces cerevisiae (S. cerevisiae). We demonstrated that liposomes prepared from S.

Vaccination with 73kDa recombinant heavy chain myosin generates high level of protection against Brugia malayi challenge in jird and mastomys models.

We have earlier reported identification, expression and purification of a 2.0kb cDNA clone coding for Brugia malayi heavy chain myosin which exhibited strong immuno-reactivity with bancroftian sera from endemic normal (EN) human subjects which are considered to be putatively immune. In the present study, immunoprophylactic characterization of B.

Wuchereria bancrofti: effect of single and multiple larval inoculations on infection dynamics and development of clinical manifestations in non-human primate Presbytis entellus.

We earlier reported the successful experimental transmission of Wuchereria bancrofti from humans to the Indian leaf monkey (Presbytis entellus) [Misra, S., Tyagi, K., Chatterjee, R.

Use of liposomized tetracycline in elimination of Wolbachia endobacterium of human lymphatic filariid Brugia malayi in a rodent model.

Wolbachia bacteria, being filarial parasite symbiont have been implicated in a variety of roles, including development, fecundity and the pathogenesis of the filarial infections. Among various strategies used in the treatment of experimental filariasis, the elimination of symbiont Wolbachia seem to offer an efficient means of curing the disease. The antiwolbachial property of tetracycline has been well worked out; however, treatment needs to be continued for a prolonged period of time to achieve complete elimination of Wolbachia from the filarial parasites and their subsequent killing.