Efficacy of a novel intradermal Lawsonia intracellularis vaccine in pigs against experimental infection and under field conditions

Background The efficacy of a novel inactivated intradermal Lawsonia intracellularis vaccine, Porcilis® Lawsonia ID, was evaluated in two experimental vaccination-challenge studies and under field conditions on a farm with a history of recurrent acute ileitis. In addition, the efficacy of the vaccine was compared to that of a commercially available live attenuated vaccine. The novel inactivated vaccine consists of a freeze-dried antigen fraction that is dissolved just prior to use in either the adjuvant or in Porcilis® PCV ID; an existing intradermal vaccine against porcine Circovirus type 2. In the two experimental vaccination-challenge studies, groups of 25 piglets were vaccinated once at 3 weeks of age or left unvaccinated as challenge control. Vaccines tested were Porcilis® Lawsonia ID as standalone (study 1) or in associated mixed use with Porcilis® PCV ID (study 2) and an orally administered commercially available live vaccine (study 1). The pigs were challenged with virulent L. intracellularis at 4 weeks (study 1) or 21 weeks (study 2) after vaccination. Post-challenge, the pigs were evaluated for clinical signs, average daily weight gain, shedding and macroscopic as well as microscopic immuno-histological ileum lesion scores. In the field study, the mortality and key performance parameters were evaluated over a period of 8 months. Results The results of the two experimental vaccination-challenge studies showed that Porcilis® Lawsonia ID as single vaccine or in associated mixed use with Porcilis® PCV ID, induced statistically significant protection against experimental L. intracellularis infection, 4 weeks or 21 weeks after vaccination. This was demonstrated by lower clinical scores, improved weight gain, reduction of L. intracellularis shedding and reduction of macroscopic as well as microscopic ileum lesion scores when compared to the controls. The protection induced was superior to that of the commercially available live vaccine. In the field study Porcilis® Lawsonia ID was highly efficacious in reducing L. intracellularis associated mortality and improving key production parameters. Conclusion The results support that this new intradermal vaccine is efficacious against L. intracellularis and may be used in associated mixed use with Porcilis® PCV ID.

Alternative Methods of Vaccine Delivery: An Overview of Edible and Intradermal Vaccines

Vaccines are recognized worldwide as one of the most important tools for combating infectious diseases. Despite the tremendous value conferred by currently available vaccines toward public health, the implementation of additional vaccine platforms is also of key importance. In fact, currently available vaccines possess shortcomings, such as inefficient triggering of a cell-mediated immune response and the lack of protective mucosal immunity. In this regard, recent work has been focused on vaccine delivery systems, as an alternative to injectable vaccines, to increase antigen stability and improve overall immunogenicity. In particular, novel strategies based on edible or intradermal vaccine formulations have been demonstrated to trigger both a systemic and mucosal immune response. These novel vaccination delivery systems offer several advantages over the injectable preparations including self-administration, reduced cost, stability, and elimination of a cold chain. In this review, the latest findings and accomplishments regarding edible and intradermal vaccines are described in the context of the system used for immunogen expression, their molecular features and capacity to induce a protective systemic and mucosal response.

The adjuvant GLA-AF enhances human intradermal vaccine responses

Adjuvants are key to shaping the immune response to vaccination, but to date, no adjuvant suitable for human use has been developed for intradermal vaccines. These vaccines could be self-administered and sent through the mail as they do not require long needles or technical expertise in immunization. In the event of a pandemic outbreak, this approach could alleviate the congregation of patients in health centers and thus reduce the potential of these centers to enhance the spread of lethal infection. A reliable and potent vaccine system for self-administration would provide an effective countermeasure for delivery through existing product distribution infrastructure. We report results from preclinical and clinical trials that demonstrate the feasibility of an adjuvanted, intradermal vaccine that induced single shot protection in ferrets and seroprotection in humans against one of the more lethal strains of pandemic flu, Indonesia H5N1. In the human trial, the vaccine was safe and clinical responses were above approvable endpoints for a protective flu vaccine. Inclusion of a modern TLR4 (Toll-like receptor 4) agonist–based adjuvant was critical to the development of the response in the intradermal groups. In humans, this is the first report of a safe and effective intradermal adjuvant, GLA-AF (aqueous formulation of glucopyranosyl lipid adjuvant), and provides a future path for developing a vaccine-device combination for distribution by mail and self-administration in case of a pandemic.

Comparison of the Immunogenicity and Safety of the Conventional Subunit, MF59-Adjuvanted, and Intradermal Influenza Vaccines in the Elderly

ABSTRACTThe influenza vaccination is known as the most effective method for preventing influenza infection and its complications in the elderly. Conventional subunit (Agrippal S1; Novartis), MF59-adjuvanted (Fluad; Novartis), and intradermal (IDflu15; Sanofi Pasteur) influenza vaccines are widely used throughout South Korea. However, few comparative studies evaluating the safety and immunogenicity of these vaccines are available. Prior to the beginning of the 2011-2012 influenza season, 335 healthy elderly volunteers randomly received one of three seasonal trivalent influenza vaccines, the conventional subunit, MF59-adjuvanted, or intradermal influenza vaccine. Serum hemagglutination-inhibiting antibody levels were measured at the time of vaccination and at 1 and 6 months after vaccination. Adverse events were recorded prospectively. A total of 113 conventional subunit, 111 MF59-adjuvanted, and 111 intradermal influenza vaccine volunteers were followed up during a 6-month postvaccination period. One month after vaccination, all three vaccines satisfied Committee for Medical Products for Human Use (CHMP) immunogenicity criteria for the A/H1N1 and A/H3N2 strains but not for the B strain. Compared with the subunit vaccine, the intradermal vaccine exhibited noninferiority, while the MF59-adjuvanted vaccine exhibited superiority. Furthermore, the MF59-adjuvanted vaccine was more immunogenic against the A/H3N2 strain than was the subunit vaccine up to 6 months postvaccination. The most common local and systemic reactions to the conventional subunit, MF59-adjuvanted, and intradermal influenza vaccines were pain at the injection site (7.1%, 10.8%, and 6.3%, respectively) and generalized myalgia (0.9%, 8.1%, and 5.4%, respectively). Local and systemic reactions were similar among the three vaccine groups. MF59-adjuvanted vaccine exhibited superior immunogenicity compared with a conventional subunit vaccine and had a comparable safety profile. For older adults, the MF59-adjuvanted vaccine is preferable for providing superior immunogenicity.