Approach For Vaccine Delivery Research Articles

P04-21. Different human serum antibody profiles elicited by three candidate HIV vaccines using different immunization approaches

Background Study and direct comparison of HIV-1 Env specific antibody responses elicited by HIV vaccines can provide useful information to identify vaccine candidates in early stage trials with greater potential of providing a protective immune response. With the goal of describing qualitative differences in humoral responses elicited by disparate HIV vaccine delivery approaches, we evaluated serum samples from three independent trials: HVTN 041, a recombinant protein based vaccine; HVTN 203, a combination canarypox prime plus protein boost vaccine, and DP6-001, a DNA prime plus protein boost vaccine.

TRANSFERSOMES FOR VACCINE DELIVERY: A POTENTIAL APPROACH FOR TOPICAL IMMUNIZATION

Delivery of vaccine is a major impediment to ensuring vaccine efficacy and compliance. Existing vaccine delivery approaches have their limitations and these led to the development of novel approaches for vaccine delivery. Non-invasive vaccine delivery is in demand and for this skin appears to be a potential sites that elicit immune responses. Topical application of antigen and adjuvant directly on the skin is termed as topical vaccination. It has potential to reduce physical skin penetration by injection and provide potentially effective vaccines. In the present study novel carrier, transfersomes were used for topical delivery of tetanus toxoid (TT). Transfersomes were prepared by reverse phase evaporation method and they were evaluated for shape, size, entrapment efficiency and deformability index. Transfersomal formulation with optimal concentration of Soya phosphatidylcholine (SPC) and sodium deoxycholate (85:15 w/w) showed entrapment efficiency of 39.8±0.032 and deformability index of 16.4. In-vivo study revealed that topically given TT containing transfersomes after boosting produced immune responses (0.877±0.081) that is as good as that produced by subcutaneously given alum adsorbed TT (0.948±0.088). Furthermore, fluorescence microscopy has confirmed the bioactive delivery through the skin layers. A brief comparative study has been done with liposomes.

Chlamydial genomics and vaccine antigen discovery.

Vaccine development for Chlamydia species has progressed on several research fronts, including knowledge of the components of the immune response required for immunity and resolution of infection as well as effective modes of delivery. The antigens required to elicit protective immune responses have not been identified. The full biologic potential for Chlamydia trachomatis and Chlamydia pneumoniae was exposed by the completion of the genome sequence for each organism. This knowledge will aid vaccine antigen discovery by facilitating the identification, testing, and evaluation of antigens by way of vaccine delivery approaches that elicit protective immunity.

Recombinant vaccinia viruses and gene gun vectors expressing the large subunit of Schistosoma mansoni calpain used in a murine immunization-challenge model

Schistosomiasis is a parasitic disease affecting over 200 million people every year in tropical regions of the world. Drug treatment and other existing control measures are costly and have failed to eliminate the incidence of infection, morbidity and mortality due to Schistosoma mansoni infection. Vaccination of susceptible individuals using recombinant vaccines encoding key S. mansoni antigens may be the most effective and least expensive means of controlling schistosomiasis. A candidate vaccine antigen is p80, the large subunit of the S. mansoni protease, calpain. In our vaccine studies, we have employed both the wild-type p80 and a mutant p80 (mut p80) in which an active site amino acid was genetically altered to create a less proteolytically-active enzyme. Two vaccine delivery approaches were implemented using p80 or mut p80 as vaccine antigen: recombinant vaccinia virus (RVV) inoculation and DNA immunization via the Accell® gene gun (GG) delivery system. RVV's expressing p80 and mut p80 were generated and tested for recombinant protein expression in vitro. These RVV's were tested for protective capacity in mouse challenge studies. Neither subcutaneous nor intranasal vaccinations with RVV-p80 or RVV-mut p80 were capable of significantly reducing the mean worm burdens of vaccinated mice. A GG-RVV combination immunization regime using WRG-vectors encoding p80 and mut p80 for GG priming and the RVV's for boosting prior to S. mansoni challenge infection was performed and no significant protection was obtained over two repeated studies. However, duplicate challenge studies involving GG immunization of mice with WRG-vectors encoding p80 or mut p80 revealed that 3 inoculations of mice with WRG-full5′ mut p80 (containing the full 5′ untranslated region of mut p80) provided 60% protection which was statistically significant ( p<0.05). These preliminary in vivo studies demonstrate the potential for further study of the protection afforded by gene gun-delivered WRG-full5′ mut p80 into subsequently-challenged mice. Such studies may pave the way to effective vaccination of humans using WRG DNA vectors expressing a schistosomal calcium-activated neutral protease.

Fully mobilizing host defense: building better vaccines.

Developments in methods for identifying antigens from infectious agents and cancers has provided exciting new opportunities in prevention and treatment through vaccination. In many of these situations, however, traditional immunization techniques do not stimulate protective immunity because they fail to fully mobilize the appropriate immune responses. This limitation, together with new insights into the underlying mechanism of immune responses, has spurred development of several new approaches for vaccine delivery. We discuss some of the current efforts being developed to provide effective vaccine delivery systems.