Evaluation of a recombinant human gelatin as a substitute for a hydrolyzed porcine gelatin in a refrigerator-stable Oka/Merck live varicella vaccine

Background  

The labile nature of live, attenuated varicella-zoster virus (Oka/Merck) requires robust stabilization during virus bulk preparation and vaccine manufacturing in order to preserve potency through storage and administration. One stabilizing ingredient used in a varicella-zoster virus (VZV) vaccine is hydrolyzed porcine gelatin which represents the major protein/peptide-based excipient in the vaccine formulation.     

Development of a model of focal pneumococcal pneumonia in young rats

Background  

A recently licensed pneumococcal conjugate vaccine has been shown to be highly effective in the prevention of bacteremia in immunized children but the degree of protection against pneumonia has been difficult to determine.     

Evaluation of recombinant invasive, non-pathogenic Eschericia coli as a vaccine vector against the intracellular pathogen, Brucella

Background  

There is no safe, effective human vaccine against brucellosis. Live attenuated Brucella strains are widely used to vaccinate animals. However these live Brucella vaccines can cause disease and are unsafe for humans. Killed Brucella or subunit vaccines are not effective in eliciting long term protection. In this study, we evaluate an approach using a live, non-pathogenic bacteria (E. coli) genetically engineered to mimic the brucellae pathway of infection and present antigens for an appropriate cytolitic T cell response.     

Assessment of immune response to repeat stimulation with BCG vaccine using in vitro PBMC model

Background  

Tuberculosis (TB) is one of the most prevalent cause of death due to a single pathogen. Bacillus Calmette Guérin (BCG) is the only vaccine available for clinical use that protects against miliary TB; however, this vaccine has shown variable levels of efficacy against pulmonary TB. In India, a single dose of BCG vaccine is given and there are few countries where repeated doses of BCG are given. The incidence of TB in India is very high inspite of primary vaccination in neonatal period and therefore requires consideration for repeated immunization.     

PCEP enhances IgA mucosal immune responses in mice following different immunization routes with influenza virus antigens

Background  

We previously demonstrated that polyphosphazenes, particularly PCEP, enhance immune responses in mice immunized subcutaneously and intranasally. The objective of the present study was to investigate the efficacy of polyphosphazenes as adjuvants when delivered through different routes of vaccine administration.     

CpG increases vaccine antigen-specific cell-mediated immunity when administered with hepatitis B vaccine in HIV infection

Background  

Lack of adequate adjuvancy is a possible explanation for lack of vaccine immunogenecity. Immunostimulatory CpGs are potent vaccine adjuvants and may be an important component of the development vaccines, particularly those for which a cellular immune response is required for protection. We have previously demonstrated that CpG ODN co-administration with hepatitis B vaccine results in earlier, stronger and more sustained antibody responses to hepatitis B surface antigen in HIV infected individuals, and wished to determine if, in this population, helper T-cell responses were also enhanced.     

Prior exposure to an attenuated <Emphasis Type="Italic">Listeria</Emphasis> vaccine does not reduce immunogenicity: pre-clinical assessment of the efficacy of a <Emphasis Type="Italic">Listeria</Emphasis>vaccine in the induction of immune responses against HIV

Background  

We have evaluated an attenuated Listeria monocytogenes (Lm) candidate vaccine vector in nonhuman primates using a delivery regimen relying solely on oral vaccination. We sought to determine the impact of prior Lm vector exposure on the development of new immune responses against HIV antigens.     

Phytol-based novel adjuvants in vaccine formulation: 2. assessment of efficacy in the induction of protective immune responses to lethal bacterial infections in mice

Background  

Adjuvants are known to significantly enhance vaccine efficacy. However, commercial adjuvants often have limited use because of toxicity in humans. The objective of this study was to determine the comparative effectiveness of a diterpene alcohol, phyto l and its hydrogenated derivative PHIS-01, relative to incomplete Freund's adjuvant (IFA), a commonly used adjuvant in augmenting protective immunity in mice against E. coli and S. aureus, and in terms of inflammatory cytokines.     

Age-related waning of in vitro Interferon-γ levels against r32kDaBCG in BCG vaccinated children

Background  

Mycobacterium bovis BCG vaccine has displayed inconsistent efficacy in different trials conducted in various geographical regions. Nevertheless, it significantly reduces the risk of severe childhood tuberculosis and continues to be used to prevent tuberculosis in many countries. Many studies revealed that efficacy of vaccine wanes with age. Most of the studies were based on in vivo and in vitro responses to tuberculin. With the advent of newer tests such as in vitro interferon-γ assays and identification of potent immunogenic mycobacterial proteins there is a need to corroborate the observations. This study aims at ascertaining the need for a booster at a later age as indicated by in vitro release of IFN-γ while evaluating Ag85A as an antigen.     

Formulation of a killed whole cell pneumococcus vaccine - effect of aluminum adjuvants on the antibody and IL-17 response

Background

Streptococcus pneumoniae causes widespread morbidity and mortality. Current vaccines contain free polysaccharides or protein-polysaccharide conjugates, and do not induce protection against serotypes that are not included in the vaccines. An affordable and broadly protective vaccine is very desirable. The goal of this study was to determine the optimal formulation of a killed whole cell pneumococcal vaccine with aluminum-containing adjuvants for intramuscular injection.

Methods

Four aluminium-containing adjuvants were prepared with different levels of surface phosphate groups resulting in different adsorptive capacities and affinities for the vaccine antigens. Mice were immunized three times and the antigen-specific antibody titers and IL-17 responses in blood were analyzed.

Results

Although all adjuvants induced significantly higher antibody titers than antigen without adjuvant, the vaccine containing aluminum phosphate adjuvant (AP) produced the highest antibody response when low doses of antigen were used. Aluminum hydroxide adjuvant (AH) induced an equal or better antibody response at high doses compared with AP. Vaccines formulated with AH, but not with AP, induced an IL-17 response. The vaccine formulated with AH was stable and retained full immunogenicity when stored at 4°C for 4 months.

Conclusions

Antibodies are important for protection against systemic streptococcal disease and IL-17 is critical in the prevention of nasopharyngeal colonization by S. pneumoniae in the mouse model. The formulation of the whole killed bacterial cells with AH resulted in a stable vaccine that induced both antibodies and an IL-17 response. These experiments underscore the importance of formulation studies with aluminium containing adjuvants for the development of stable and effective vaccines.     

Pattern of distribution and cycling of SLOB,Slowpoke channel binding protein,in <Emphasis Type="Italic">Drosophila</Emphasis>

Background  

SLOB binds to and modulates the activity of the Drosophila Slowpoke (dSlo) calcium activated potassium channel. Recent microarray analyses demonstrated circadian cycling of slob mRNA.     

Neuroprotective effects of edaravone-administration on 6-OHDA-treated dopaminergic neurons

Background

A recent human clinical trial of an Alzheimer's disease (AD) vaccine using amyloid beta (Aβ) 1–42 plus QS-21 adjuvant produced some positive results, but was halted due to meningoencephalitis in some participants. The development of a vaccine with mutant Aβ peptides that avoids the use of an adjuvant may result in an effective and safer human vaccine.

Results

All peptides tested showed high antibody responses, were long-lasting, and demonstrated good memory response. Epitope mapping indicated that peptide mutation did not lead to epitope switching. Mutant peptides induced different inflammation responses as evidenced by cytokine profiles. Ig isotyping indicated that adjuvant-free vaccination with peptides drove an adequate Th2 response. All anti-sera from vaccinated mice cross-reacted with human Aβ in APP/PS1 transgenic mouse brain tissue.

Conclusion

Our study demonstrated that an adjuvant-free vaccine with different Aβ peptides can be an effective and safe vaccination approach against AD. This study represents the first report of adjuvant-free vaccines utilizing Aβ peptides carrying diverse mutations in the T-cell epitope. These largely positive results provide encouragement for the future of the development of human vaccinations for AD.     

Diversity-oriented, one-pot, multi-component synthesis of substituted uracil derivatives

Abstract  

With the emergence of high throughput screening of bioactive molecules, there is constant need for the development of new strategies for diversity-oriented synthesis. We describe here a novel one-pot multicomponent reaction for the synthesis of uracil derivatives using easily available starting materials. This new synthetic strategy provides easy access to diverse uracil derivatives in moderate to good yields.     

Three-component reactions of isocyanides, dialkyl acetylenedicarboxylates, and trans-cinnamoyl chlorides for the synthesis of highly functionalized 2-vinyl furans

Abstract  

In this study, we present a convenient and efficient method for the synthesis of novel, highly substituted 2-vinyl furans using a three-component reaction. The zwitterions generated from the reaction of isocyanides and dialkyl acetylenedicarboxylates are reacted with trans-cinnamoyl chlorides to produce the desired products in good yields.     

Expressions of glutathione S-transferase alpha,mu, and pi in brains of medically intractable epileptic patients

Background  

Glutathione S-transferases (GSTs) play an important role in metabolizing anti-epileptic drugs (AEDs) in liver. Expressions of GSTs in brain, which may result in poor efficacy of AEDs, have not been well studied. Using clinical cortex specimen from 32 intractable epileptic subjects and 8 non-epileptic controls, the present study investigated the correlation between GSTs and intractable epilepsy.     

Central administration of dipeptides,beta-alanyl-BCAAs,induces hyperactivity in chicks

Background  

Carnosine (β-alanyl-L-histidine) is a putative neurotransmitter and has a possible role in neuron-glia cell interactions. Previously, we reported that carnosine induced hyperactivity in chicks when intracerebroventricularly (i.c.v.) administered. In the present study, we focused on other β-alanyl dipeptides to determine if they have novel functions.     

Common cortical responses evoked by appearance, disappearance and change of the human face

Background  

To segregate luminance-related, face-related and non-specific components involved in spatio-temporal dynamics of cortical activations to a face stimulus, we recorded cortical responses to face appearance (Onset), disappearance (Offset), and change (Change) using magnetoencephalography.     

Effect of neutrophil depletion on gelatinase expression,edema formation and hemorrhagic transformation after focal ischemic stroke

Background  

While gelatinase (MMP-2 and -9) activity is increased after focal ischemia/reperfusion injury in the brain, the relative contribution of neutrophils to the MMP activity and to the development of hemorrhagic transformation remains unknown.     

Plexin B3 promotes neurite outgrowth,interacts homophilically,and interacts with Rin

Background  

Plexins, known to date as receptors of semaphorins, are implicated in semaphorin-mediated axon repulsion and growth cone collapse. However, subtype-specific functions of the majority of the nine members of the mammalian plexin family are largely unknown. In order to investigate functional properties of B-plexins, we analyzed the expression of human and murine plexin B3 and expressed full-length human plexins B2 (B2) and B3 (B3) in NIH-3T3 cells.