Adjuvants have been considered for a long time to be an accessory and empirical component of vaccine formulations. However, accumulating evidence of their crucial role in initiating and directing the immune response has increased our awareness of the importance of adjuvant research in the past decade. Nevertheless, the importance of adjuvants still is not fully realized by many researchers working in the vaccine field, who are involved mostly in the search for better target antigens. The choice of a proper adjuvant can be determinant for obtaining the best results for a given vaccine candidate, but it is restricted due to intellectual property and know-how issues. Consequently, in most cases the selected adjuvant continues to be the aluminum salt, which has a record of safety, but predominantly constitutes a delivery system (DS). Ideally, new strategies should combine immune potentiators (IP) and DS by mixing both compounds or by obtaining structures that contain both IP and DS. In addition, the term immune polarizer has been introduced as an essential concept in the vaccine design strategies. Here, we review the theme, with emphasis on the discussion of the few licensed new adjuvants, the need for safe mucosal adjuvants and the adjuvant/immunopotentiating activity of conjugation. A summary of toxicology and regulatory issues will also be discussed, and the Finlay Adjuvant Platform is briefly summarized.
Neisseria meningitidis B proteoliposome (AFPL1 when used as adjuvant) and its derivative‐Cochleate (AFCo1) contain immunopotentiating and immunomodulating properties and delivery system capacities required for a good adjuvant. Additionally, they contain meningococcal protective antigens and permit packaging of other antigens and pathogen‐associated molecular patterns (PAMP). Consequently, we hypothesized that they would function as good vaccine adjuvants for their own antigens and also for non‐related antigens. AFPL1 is a detergent‐extracted outer membrane vesicle of N. meningitidis B transformed into AFCo1 in calcium environment. Both are produced at Finlay Institute under good manufacture practices (GMP) conditions. We show their exceptional characteristics: combining in the same structure, the potentiator activity, polarizing agents and delivery system capacities; presenting multimeric protein copies; containing multiprotein composition and multi and synergistic PAMP components; acting with incorporated or co‐administrated antigens; inducing type I IFN‐γ and IL‐12 cytokines suggesting the stimulation of human plasmocytoid precursor and conventional dendritic cells, respectively, inducing a preferential Th1 immune response with TCD4+, TCD8+, cross‐presentation and cytotoxic T‐lymphocyte (CTL) in vivo responses; and functioning by parenteral and mucosal routes. AFPL1–AFCo1 protective protein constitutions permit per se their function as a vaccine. In addition to Phase IV Men BC vaccine, AFPL1 has ended the preclinical stage in an allergy vaccine and is concluding the preclinical stage of a nasal meningococcal vaccine. In conclusion, AFPL1 and AFCo1 induced signal 1, 2 and 3 polarizing to a Th1 (including CTL) response when they acted directly as vaccines or were used as adjuvants with incorporated or co‐administered antigens by parenteral or mucosal routes. Both are very promising adjuvants.
Pork has been traditionally considered an important source of human Toxoplasma gondii infection. Pigs, as other meat-producing animals, can become infected by the ingestion of oocysts that are shed in the environment by infected cats or by the consumption of cysts present in tissues of infected mammals, commonly small rodents. The objective of this study was to investigate the level of T. gondii infection in swine from southern Chile that can be associated with the ingestion of oocysts and therefore exposure to a contaminated environment. A total of 340 serum samples from swine were obtained from three commercial slaughterhouses located in the Araucania and Los Rios Regions from southern Chile. Study animals originated from local farms, mainly small commercial producers, and the meat is sold locally. Overall, 8.8% (30/340) of the samples showed T. gondii-specific IgG antibodies. Of these sero-positive animals, 80% (24/30) were also positive for antibodies specific against the oocyst stage of the parasite, indicating that animals had been infected recently by the ingestion of oocysts. The observed results suggest a high level of environmental contamination with oocysts on the farms of origin. In addition to the food safety problems associated with the consumption of meat from infected animals, the high level of environmental contamination on the farm represents a direct health risk for people living and/or working on these farms. Consequently, there is a need to develop on-farm monitoring programmes and identify risk reduction strategies (food storage, water purification, rodent control and contact with cats) that are appropriate and cost-effective for informal and outdoor type of farms.
Increasing emphasis is being placed on the mucosal administration of vaccines in order to stimulate mucosal as well as systemic responses. Findings from our group suggest that proteoliposome-derived cochleate (AFCo1) acts as a potent mucosal adjuvant. As an alternative to chemical conjugation, the current study aimed to determine the benefit of using AFCo1 to improve the mucosal and systemic immune responses to capsular polysaccharide of Neisseria meningitidis serogroup C (PsC), a model of a thymus-independent (TI) antigen. Therefore, intranasal (i.n.) immunization of 3 doses 1 week apart with AFCo1 plus PsC in mice was conducted. Highly specific anti-PsC IgA responses and an anti-PsC IgG response were obtained. The subclass pattern induced against PsC was similar to that induced with the meningococcal vaccine. In summary, AFCo1 as nasal adjuvant was demonstrated to be capable of eliciting mucosal and systemic specific responses against a TI antigen.
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