A Bordetella pertussis proteoliposome induces protection in mice without affecting the immunogenicity of diphtheria and tetanus toxoids in a trivalent formulation

In this study, a formulation of Bordetella pertussis proteoliposome (PLBp), diphtheria, and tetanus toxoids and alum (DT-PLBp) was evaluated as a trivalent vaccine candidate in BALB/c mice. Vaccine-induced protection was estimated using the intranasal challenge for pertussis and enzyme-linked immunosorbent assay fvto assess serological responses for diphtheria or tetanus. Both, diphtheria-tetanus-whole cell pertussis (DTP) and diphtheria-tetanus vaccines (DT) were used as controls. Animals immunized with DT-PLBp, PLBp alone, and DTP showed total reduction of CFU in lungs 7 days after intranasal challenge. Likewise, formulations DT-PLBp, DTP, and DT elicited antibody levels ≥2 IU/mL against tetanus and diphtheria, considered protective when neutralization tests are used. Overall, results showed that combination of PLBp with tetanus and diphtheria toxoids did not affect the immunogenicity of each antigen alone.

The expanding role of immunopharmacology: IUPHAR Review 16.

Drugs targeting the immune system such as corticosteroids, antihistamines and immunosuppressants have been widely exploited in the treatment of inflammatory, allergic and autoimmune disorders during the second half of the 20th century. The recent advances in immunopharmacological research have made available new classes of clinically relevant drugs. These comprise protein kinase inhibitors and biologics, such as monoclonal antibodies, that selectively modulate the immune response not only in cancer and autoimmunity but also in a number of other human pathologies. Likewise, more effective vaccines utilizing novel antigens and adjuvants are valuable tools for the prevention of transmissible infectious diseases and for allergen-specific immunotherapy. Consequently, immunopharmacology is presently considered as one of the expanding fields of pharmacology. Immunopharmacology addresses the selective regulation of immune responses and aims to uncover and exploit beneficial therapeutic options for typical and non-typical immune system-driven unmet clinical needs. While in the near future a number of new agents will be introduced, improving the effectiveness and safety of those currently in use is imperative for all researchers and clinicians working in the fields of immunology, pharmacology and drug discovery. The newly formed ImmuPhar (http://iuphar.us/index.php/sections-subcoms/immunopharmacology) is the Immunopharmacology Section of the International Union of Basic and Clinical Pharmacology (IUPHAR, http://iuphar.us/). ImmuPhar provides a unique international expert-lead platform that aims to dissect and promote the growing understanding of immune (patho)physiology. Moreover, it challenges the identification and validation of drug targets and lead candidates for the treatment of many forms of debilitating disorders, including, among others, cancer, allergies, autoimmune and metabolic diseases.

Validation of a new alternative for determining in vitro potency in vaccines containing Hepatitis B from two different manufacturers.

Facing the discontinuation of the Auszyme kit, an alternative is needed for determining the in vitro potency of Hepatitis B surface antigen in vaccines. An inhibition ELISA has already proven to be reliable, but not in vaccine combinations. We validated this method by the evaluation of monovalent and combined vaccines from two different manufacturers. All validation parameters fulfilled the defined acceptance criteria. There was some interference with Hepatitis B potency, mainly produced by the whole cell Pertussis component, but it was not significant. A significant correlation between the Auszyme kit and the in vivo method was observed. We demonstrated that our ELISA is suitable for evaluating HB antigen in vaccines and could be considered as a potential alternative to the Auszyme kit.

Relationships among physico-chemical and biological tests for a synthetic Hib-TT conjugate vaccine.

The relationships among physico-chemical and biological tests were evaluated in this study for Cuban Hib vaccine, a tetanus toxoid conjugated with a polysaccharide obtained from chemical synthesis, in order to estimate the biological significance of the relevant physico-chemical assays for lot released. In order to get samples with theoretical different potencies, Hib-TT samples were stored at -20, 4, 25, 37 and 70 degrees C for 5 weeks and after they were evaluated by HPLC and Orcinol methods and for immunogenicity and bactericidal activity. We found strong relationships between HPLC and free PRP level (r2=0.9571), anti-PRP antibodies and bactericidal activity (r2=0.9649) and free PRP content and anti-PRP antibodies titres (r2=0.7671). A lower correlation was found for HPLC and anti-PRP titres (r2=0.5996). We demonstrate that it is possible to monitor this new product combining physico-chemical and biological tests in order to contribute to its characterisation.

Comparison between in vitro potency tests for Cuban hepatitis B vaccine: contribution to the standardization process.

Quality control of recombinant Hepatitis B vaccines performed by National Control Laboratories prior to marketing vaccine batches requires in vivo and or a well validated in vitro potency assays as recommended by WHO technical series. The in vitro test must also demonstrate its suitability for monitoring the consistency of the vaccine manufacturer. The aim of this study was to establish the relationship between both in vitro potency tests performed by Cuban manufacturer and National Control Laboratory for Hepatitis B vaccine and the suitability of our method for monitoring the manufacturer's test results and consistency. We also intended to contribute to the standardisation process consisting of in vitro methods for this vaccine.