Use of adjuvant containing pathogen pattern recognition receptor agonists is one of the effective strategies to enhance the efficacy of licensed vaccines. In this study, we investigated the efficacy of avian influenza vaccines containing an adjuvant (CVCVA5) which was composed of polyriboinosinic polyribocytidylic, resiquimod, imiquimod, muramyl dipeptide and levomisole. Avian influenza vaccines adjuvanted with CVCVA5 were found to induce significantly higher titers of hemagglutiniton inhibition antibodies (P ≤ 0.01) than those of commercial vaccines at 2-, 3- and 4-week post vaccination in both specific pathogen free (SPF) chickens and field application. Furthermore, virus shedding was reduced in SPF chickens immunized with H9-CVCVA5 vaccine after H9 subtype heterologous virus challenge. The ratios of both CD3+CD4+ and CD3+CD8+ lymphocytes were slowly elevated in chickens immunized with H9-CVCVA5 vaccine. Lymphocytes adoptive transfer study indicates that CD8+ T lymphocyte subpopulation might have contributed to improved protection against heterologous virus challenge. Results of this study suggest that the adjuvant CVCVA5 was capable of enhancing the potency of existing avian influenza vaccines by increasing humoral and cellular immune response.

Once excessive, neurological disorders associated with inflammatory conditions will inevitably cause secondary inflammatory damage to brain tissue. Immunosuppressive therapy can reduce the inflammatory state, but resulting infections can expose the patient to greater risk. Using specific immune tolerance organs or tissues from the body, brain antigen immune tolerance treatment can create a minimal immune response to the brain antigens that does not excessively affect the body's immunity. However, commonly used immune tolerance treatment approaches, such as those involving the nasal, gastrointestinal mucosa, thymus or liver portal vein injections, affect the clinical conversion of the therapy due to uncertain drug absorption, or inconvenient routes of administration. If hepatic portal intravenous injections of brain antigens could be replaced by normal peripheral venous infusion, the convenience of immune tolerance treatment could certainly be greatly increased. We attempted to encapsulate brain antigens with minimally immunogenic nanomaterials, to control the sizes of nanoparticles within the range of liver Kupffer cell phagocytosis and to coat the antigens with a coating material that had an affinity for liver cells. We injected these liver drug-loaded nanomaterials via peripheral intravenous injection. With the use of microparticles with liver characteristics, the brain antigens were transported into the liver out of the detection of immune armies in the blood. This approach has been demonstrated in rat models of surgical brain injury. It has been proven that the immune tolerance of brain antigens can be accomplished by peripheral intravenous infusion to achieve the effect of treating brain trauma after operations, which simplifies the clinical operation and could elicit substantial improvements in the future.

Oral administration of myelin antigens reduces the incidence and severity of EAE in rat and mouse models and decreases the frequency of MBP-reactive cells and the frequency of attacks in some patients with multiple sclerosis. Low-dose oral tolerance has been shown to be mediated by Th2-type regulatory cells that secrete TGFbeta and IL-4/IL-10. Adjuvants and cytokines may modulate oral tolerance. The addition of betaIFN to the experimental therapy regimen, either orally or by intraperitoneal injection, has been shown to enhance the suppressive effects of oral myelin antigens when either are fed the suboptimal dosing regimen to suppress EAE. The current studies were conducted to elucidate the mechanism of the observed in vivo synergy of betaIFN and antigen feeding. Analysis of the in vitro proliferative response and cytokine production by lymphocytes from fed animals in response to specific antigen in culture shows that the synergistic effect may be related to both independent suppression of the immune response by oral betaIFN and enhanced production of TGFbeta and IL-4/IL-10. There was an unexpected increase in the production of gammaIFN by lymphocytes in vitro after three doses of oral betaIFN in vivo. These observations have important implications for the use of cytokines to modulate oral tolerance.