Mucosal and systemic immune responses induced by a single time vaccination strategy in mice.

Vaccination is considered by the World Health Organization as the most cost-effective strategy for controlling infectious diseases. In spite of great successes with vaccines, many infectious diseases are still leading killers, because of the inadequate coverage of many vaccines. Several factors have been responsible: number of doses, high vaccine reactogenicity, vaccine costs, vaccination policy, among others.

Adjuvants are Key Factors for the Development of Future Vaccines: Lessons from the Finlay Adjuvant Platform.

The development of effective vaccines against neglected diseases, especially those associated with poverty and social deprivation, is urgently needed. Modern vaccine technologies and a better understanding of the immune response have provided scientists with the tools for rational and safer design of subunit vaccines. Often, however, subunit vaccines do not elicit strong immune responses, highlighting the need to incorporate better adjuvants; this step therefore becomes a key factor for vaccine development.

[In silico identification of molecular mimicry between T-cell epitopes of Neisseria meningitidis B and the human proteome].

The objective of the study was to determine the T-cell epitopes of four of the most frequent antigenic proteins of the outer membrane of Neisseria meningitidis B, and to identify the most relevant sites for molecular mimicry with T-cell epitopes in humans. In order to do so, an in silico study -a type of study that uses bioinformatic tools- was carried out using SWISS-PROT/TrEMBL, SYFPEITHI and FASTA databases, which helped to determine the protein sequences, CD4 and CD8 T-cell epitope prediction, as well as the molecular mimicry with humans, respectively. Molecular similarity was found in several human proteins present in different organs and tissues such as: liver, skin and epithelial tissues, brain, lymphatic system and testicles.

Pilot scale production of the vaccine adjuvant Proteoliposome derived Cochleates (AFCo1) from Neisseria meningitidis serogroup B.

The use of new adjuvants in vaccine formulations is a subject of current research. Only few parenteral adjuvants have been licensed. We have developed a mucosal and parenteral adjuvant known as AFCo1 (Adjuvant Finlay Cochleate 1, derived from proteoliposomes of N.

The golden era of vaccine adjuvants.

A 5-day workshop on adjuvant for vaccines was held in Trinidad, Cuba, on the 16-21 May 2010. Organized by the Latin American Association for Immunology and the Cuban Society for Immunology, the workshop attracted more than 60 scientists from different parts of the world. The meeting summarizes current knowledge regarding vaccine adjuvants, including delivery systems and parasitic vaccines.

AFCo1 as nasal adjuvant of capsular polysaccharide from Neisseria meningitidis serogroup C induces systemic and mucosal immune responses.

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.

Mucosal and systemic immune responses of mice to tetanus toxoid coadministered nasally with AFCo1.

Mucosal immune responses are an early and important line of defense against pathogens. The current understanding of the mucosal immune system allows us to consider the use of nasal immunization for induction of antigen-specific immune responses at the mucosal surface and the systemic compartment. Mucosal adjuvants are key for developing novel mucosal vaccines and represent 1 approach to improving mucosal and systemic immunity.

Mucosal immunization using proteoliposome and cochleate structures from Neisseria meningitidis serogroup B induce mucosal and systemic responses.

Most pathogens either invade the body or establish infection in mucosal tissues and represent an enormous challenge for vaccine development by the absence of good mucosal adjuvants. A proteoliposome-derived adjuvant from Neisseria meningitidis serogroup B (AFPL1, Adjuvant Finlay Proteoliposome 1) and its derived cochleate form (Co, AFCo1) contain multiple pathogen-associated molecular patterns as immunopotentiators, and can also serve as delivery systems to elicit a Th1-type immune response. The present studies demonstrate the ability of AFPL1and AFCo1 to induce mucosal and systemic immune responses by different mucosal immunizations routes and significant adjuvant activity for antibody responses of both structures: a microparticle and a nanoparticle with a heterologous antigen.

New meningococcal C polysaccharide-tetanus toxoid conjugate Physico-chemical and immunological characterization.

The polysaccharides (Ps) are thymus-independent 2 (TI-2) antigens and poor immunogens in infants and young children; as a result of this delayed response to Ps antigens during ontogeny, infants and young children are highly susceptible to infections caused by encapsulated bacteria. Meningococcal group C polysaccharide (PsC)-proteins conjugate vaccines have been reported to induce significant serum IgG antibodies and immunologic memory in infants resulting in very effective vaccines. We describe here the obtainment, by a new method, of a neoglycoconjugate intended to immunize against Neisseria meningitidis serogroup C, its characterization by physico-chemical methods, including (1)H NMR and fluorescence spectroscopy methods, as well as the characterization of the immune response induced in mice by such conjugate.

New method for obtaining conjugated vaccines.

We describe a new method to obtain conjugates against Neisseria meningitidis serogroups A, B, C, Vibrio cholera, and Salmonella typhi and their immunogenicity in Balb/c mice. The saccharides were activated by basic hydrolysis with the generation of amine groups in the saccharidic chain, and these groups were linked to carboxyl groups of tetanus toxoid by via carbodiimida-mediated reaction. The resultant conjugates were administered to mice for the immunogenicity studies.

Preparation and evaluation of vibrio cholerae O1 EL Tor Ogawa lipopolysaccharide-tetanus toxoid conjugates.

The lipopolysaccharide (LPS) of Vibrio cholerae is considered one of the most important antigens from the point of view of immunogenicity in these bacteria. We have undertaken detoxification of this LPS by basic hydrolysis and the resultant amine groups were used for their conjugation to tetanus toxoid as carrier protein using carbodiimide-mediated coupling. The resulting conjugates were inoculated in Balb/c mice for immunogenicity studies.

Mucosal immune responses to meningococcal C polysaccharide-protein conjugate in mice.

Mucosal delivery of vaccines represents an attractive approach because this is a region of first contact point for inhaled antigens. We have obtained a meningococcal group C polysaccharide-tetanus toxoid conjugate (MGCP-TT) and evaluated it for intranasal route in mice. The conjugate was obtained by a developed method in our laboratory.

Adjuvant properties of lipopolysaccharide from Neisseria meningitidis serogroup B detoxified and conjugated with tetanus toxoid.

We evaluated the adjuvant properties and toxicity of purified Neisseria meningitidis serogroup B lipopolysaccharide (LPS) conjugated with tetanus toxoid (TT) using a new method of conjugation to obtain amine groups in the polysaccharide structure. The endotoxic activity of treated LPS was reduced 2400 times as determined by Limulus amoebocyte assay and no mortality was observed in Balb/c mice inoculated with detoxified LPS versus 100% mortality in native LPS inoculated mice. The conjugated LPS-TT elicited in mice higher anti-TT IgG2a and IgG1 than unconjugated TT.