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.

Immunization is one of the most successful and cost-effective health interventions ever. Immunization have been helping to reduce child mortality, improving maternal health and combating infectious diseases. In spite of its, undisputed past success and promising future, however, immunization remains an unfinished agenda because of them inadequate coverage. Several factors have been largely responsible of a difficulty to attain immunization coverage and have been recognized as a problems of current vaccines, such as: the number of dose, excessive use of parenteral route, a small number of adjuvants approve for use in human, higher reactogenicity and unavailability against intracellular pathogens, infected or altered cells and scanty feasibility to combined more than one antigen in the same formulation. For bacterial meningitis WHO estimates that 1.2 million cases occur annually and Neisseria meningitidis is the etiological agent in more than 40% of these cases although some meningococcal vaccines are available. To bear in mind these principals problems, a novel protocol for vaccination against N. meningitidis called Single Time Vaccination Strategy (SinTimVaS) is proposed. Using female BALB/c mice, we induce systemic and mucosal immune responses against N. meningitidis with only one parenteral and one mucosal dose at the same time, employing the Finlay Adjuvants derivate from N. meningitidis, AFPL1 and AFCo1, respectively. In conclusion, SinTimVaS could increase the vaccination coverage and reduce the time-cost of vaccine campaigns, adding the possibility to increase the herd immunity by mucosal specific response induction.

Meningococcal B strains accounts for some 72% and 28% of meningococcal diseases in infants and toddlers in Europe and the USA, respectively. Nevertheless, meningococcal diseases are rare in Cuba owing to the wide spread program on antimeningococcal vaccination in the country. Finlay Institute is one of the pioneering organizations in Neisseria Vaccinology mainly by its contribution to N. meningitidis serogroup B outer membrane-based bivalent vaccine, VA-MENGOC-BC™. This vaccine was given intramuscularly in more than 60 million doses corresponding 10.7 millions of them to Cuban young adults, children, and infants. However, most dangerous or commensally Neisseria strains enter and establish in the mucosa, where the secretory (S) IgA is the main specific guardian and is mainly induced by mucosal routes. However, few mucosal vaccines exist principally due to the absent of mucosal adjuvants. We develop a Finlay Adjuvant (AF) platform based in outer membrane vesicles (Proteoliposome, PL) and its derivate Cochleate (Co). AFPL1 derived from serogroup B N. meningitidis is a potent Th1/CTL driving parenteral adjuvant. AFCo1 is a potent mucosal adjuvant. Therefore, we sought to go deeper in the possible mucosal cross recognition between N. meningitidis serogroups and Neisseria species and explore a concurrent mucosal and parenteral immunization strategy (SinTimVaS) in order to develop suitable mucosal vaccines. Experiments were conducted in Balb/c or C57Bl6 mice with mucosal and systemic immunization using AFCo1 and AFPL1. Human sera and saliva were also analyzed for cross cognition. Mucosal cross recognition at SIgA level in human saliva between N. meningitidis serogroups B, A, C, Y, and W135 were observed. This SIgA cross recognition response was also observed between pathogenic (N. meningitidis serogroup B, N. gonorrhoeae) and non-pathogenic strains (N. flava, N. lactamica). The possible influence of meningococcal vaccination against Gonorrhea was also explored. A proprietary Single Time Vaccination Strategy combining simultaneous mucosal and parenteral doses was developed. N. meningitidis and N. gonorrhoeae show significant cross immune response, and mucosal immunization with AFCo1 to obtain immunity against both strains may be a useful strategy to combat both infections in humans. Single Time Vaccination Strategy could be important to increased human vaccination coverage and herd immunity protecting both systemic and mucosal environments.