Vaccine Formulation for Infectious Diseases and Adjuvant Mechanisms of Action

The ultimate goal for vaccination is the generation of a safe and effective immune response that protects against diseases [...

Mucosal delivery of vaccines in domestic animals

Mucosal vaccination is proving to be one of the greatest challenges in modern vaccine development. Although highly beneficial for achieving protective immunity, the induction of mucosal immunity, especially in the gastro-intestinal tract, still remains a difficult task. As a result, only very few mucosal vaccines are commercially available for domestic animals. Here, we critically review various strategies for mucosal delivery of vaccines in domestic animals. This includes live bacterial and viral vectors, particulate delivery-systems such as polymers, alginate, polyphosphazenes, immune stimulating complex and liposomes, and receptor mediated-targeting strategies to the mucosal tissues. The most commonly used routes of immunization, strategies for delivering the antigen to the mucosal surfaces, and future prospects in the development of mucosal vaccines are discussed

Mucosal delivery of vaccines in domestic animals

International audienceMucosal vaccination is proving to be one of the greatest challenges in modern vaccine development. Although highly beneficial for achieving protective immunity, the induction of mucosal immunity, especially in the gastro-intestinal tract, still remains a difficult task. As a result, only very few mucosal vaccines are commercially available for domestic animals. Here, we critically review various strategies for mucosal delivery of vaccines in domestic animals. This includes live bacterial and viral vectors, particulate delivery-systems such as polymers, alginate, polyphosphazenes, immune stimulating complex and liposomes, and receptor mediated-targeting strategies to the mucosal tissues. The most commonly used routes of immunization, strategies for delivering the antigen to the mucosal surfaces, and future prospects in the development of mucosal vaccines are discussed

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Not AvailableMucosal delivery of CpG oligodeoxynucleotide (ODN) in mice has been shown to induce potent innate immunostimulatory responses and protection against infection. We evaluated the efficacy of CpG ODN in stimulating systemic innate immune responses in sheep following delivery to the pulmonary mucosa. Intrapulmonary (IPM) administration of B-Class CpG ODN in saline induced transient systemic responses which included increased rectal temperatures, elevated serum 2′5′-A synthetase and haptoglobin concentrations. The ODN dose required to induce detectable systemic responses following IPM delivery could be reduced by approximately 80% if the CpG ODN was administered in 30% emulsigen® instead of saline. Intrapulmonary B-Class CpG ODN formulated in 30% emulsigen produced similar effects when compared to those seen following SC injection. These responses were CpG ODN-specific since control GpC ODN did not induce any detectable response. Intrapulmonary administration of both B-Class and the newly described C-Class CpG ODN produced similar effects indicating that both classes of CpG ODN were comparably effective in stimulating innate immune system following mucosal delivery. Administration of CpG ODN directly into the lungs or delivery of CpG ODN via an intratracheal (IT) infusion also produced similar systemic responses. These observations support the conclusion that mucosal delivery of CpG ODN is an effective route for induction of systemic acute phase responses and antiviral effector molecules in large animals, and may be helpful in controlling systemic infections.Not Availabl

Immunization with PCEP microparticles containing pertussis toxoid, CpG ODN and a synthetic innate defense regulator peptide induces protective immunity against pertussis

AbstractWe investigated the efficacy of a novel microparticle (MP) based vaccine formulation consisting of pertussis toxoid (PTd), polyphosphazene (PCEP), CpG ODN 10101 and synthetic cationic innate defense regulator peptide 1002 (IDR) against Bordetella pertussis in mice. We studied whether encapsulation of these IDR-CpG ODN complexes into polyphosphazene-based microparticles further enhanced their immunomodulatory activity compared to soluble formulations containing PCEP (SOL), or without PCEP (AQ). In vitro stimulation of murine macrophages showed MP induced significantly higher levels of pro-inflammatory cytokines. When assessed in a B. pertussis infection challenge model, a single immunization with MP formulation led to significantly lower bacterial loads compared to other formulations and non-vaccinated animals. ELISPOT of splenocytes showed that MP group mice had significantly higher number of antigen-specific IL-17 secreting cells. The cytokine profile in lung homogenates of MP group mice after challenge showed significantly higher amounts of MCP-1, TNF-α, IFN-γ, IL-12 and IL-17 and significantly lowered IL-10 levels suggesting a strong Th1 shift. Protection was observed against challenge infection with B. pertussis. On the other hand protective immune responses elicited in Quadracel® immunized mice were Th2 skewed. Hence, we conclude that formulation of PTd, PCEP, CpG ODN and IDR into MP generates a protective immune response in mice against pertussis emphasizing the potential of MP as a delivery vehicle for the potential development of single-shot vaccines