Immunogenicity of a novel anti-allergic vaccine based on house dust mite purified allergens and a combination adjuvant in a murine prophylactic model.

The outer-membrane-derived proteoliposome (PL) of has been reported as a potent vaccine adjuvant, inducing a Th1-skewed response. This work aimed to assess the immunogenicity of a novel anti-allergic vaccine candidate based on allergens from house dust mite and a combination adjuvant containing PL and Alum. In a preventative experimental setting, BALB/c mice were administered with three doses containing 2 µg of Der s1 and 0.

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.

Nasal immunization of mice with AFCo1 or AFPL1 plus capsular polysaccharide Vi from Salmonella typhi induces cellular response and memory B and T cell responses.

The response to infection against Salmonella involves both B and T cell mediated immunity. An effective immunization can activate an adequate immune response capable to control the primary infection and protect against a secondary infection. Mucosal vaccination, by inducing local pathogen-specific immune responses, has the potential to counter mucosally transmitted pathogens at the portal of entry, thereby increasing the efficacy of vaccines.

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.

Combined meningococcal serogroup A and W135 outer-membrane vesicles activate cell-mediated immunity and long-term memory responses against non-covalent capsular polysaccharide A.

Outer-membrane vesicles (OMVs) have inherent adjuvant properties, and many vaccines use OMV as vaccine components. Utilizing the adjuvant properties of OMV could lead to the formulation of vaccines that are less expensive and potentially more immunogenic than covalently conjugated polysaccharide vaccines. We evaluated the adjuvant effect in Balb/c mice of combinations of OMV from Neisseria meningitidis serogroup A and W135 as compared to that of the non-covalently conjugated capsular polysaccharide A.

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.

[Immunological adjuvants. Determinant factors in the efficacy-toxicity ratio of the contemporary vaccines].

To achieve effective and safe vaccines for the prevention of not yet controlled or re-emergent infectious diseases, one of the more importance aspects is to have immunological adjuvants that allow inducing a protective immune response with an appropriate safety profile. Since 1926 the aluminium compounds have been used as adjuvants for human vaccines, and only in the last 10 years have some new products been registered. Although there an enormous quantity of proposed candidates, the toxicity is the main factor that has limited their introduction into the clinic.

Can mucosal adjuvants contribute to the induction of immunological memory induced via unconjugated T-cell-independent antigens?

Vaccination remains the most cost-effective method for preventing infectious diseases. Key to vaccine design is the development of immunological memory, which is an essential property of the adaptive immune system. Bacterial polysaccharide conjugate vaccines are the gold standard currently used to confer protection of the host by inducing humoral immune responses against T-cell-independent antigens.

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.

Intranasal administration of proteoliposome-derived cochleates from Vibrio cholerae O1 induce mucosal and systemic immune responses in mice.

Conservative estimates place the death toll from cholera at more than 100,000 persons each year. A particulate mucosal vaccine strategy combining antigens and immune stimulator molecules from Vibrio cholerae to overcome this problem is described. Proteoliposomes extracted from V.

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.

Scale up of proteoliposome derived Cochleate production.

Cochleate are highly stable structures with promising immunological features. Cochleate structures are usually obtaining from commercial lipids. Proteoliposome derived Cochleate are derived from an outer membrane vesicles of Neisseria meningitidis B.

Strategy for determination of an efficient Cochleate particle size.

Cochleate structures obtained from the outer membrane of Neisseria meningitidis serotype B have demonstrated to be high immunogenicity when administrated by intramuscular, oral or intranasal routes, and could be used as adjuvant and meningococcal nasal vaccine candidate. Due to the microparticulate nature of Cochleate it is necessary to control the particle size since it capture by cells of the immune system could be affected by this aspect. We combined optic microscopy and immunisation experiments to select the optimum particle size.

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.

Proteliposome-derived Cochleate as an immunomodulator for nasal vaccine.

Proteoliposome (PL) has been recently used as a protective intramuscular (i.m.) anti-meningococcal BC vaccine.

Immunological evaluation of bacterial derived Cochleate and proteoliposome as mucosal adjuvants.

We evaluated the potential of two bacterial derived compounds, Cochleate and Proteoliposome (PL), administrated to mice by nasal or oral routes on induction of antibody and cytokine responses. Anti PL IgG and IgA responses were measured by ELISA in saliva, sera or vaginal fluids of immunized mice. Productions of gammaIFN and IL-5 were determined in spleen cells of immunized mice following a recall in vitro with Cochleate or PL.

Bacterial derived proteoliposome for allergy vaccines.

One current approach in developing anti allergic vaccines is the use of potent adjuvants, capable of inducing Th1 or T regulatory cells. Proteoliposomes (PL) could be a suitable adjuvant. Purified Dermatophagoides siboney (Ds) allergens were mixed with PL and adsorbed into Al(OH)3 and evaluated in mice.

Proteoliposome derived cochleate as novel adjuvant.

Cochleate structures (CS) consist in a highly stable lipid structures that have been reported to be a good antigen delivery system. The incorporation of pathogen associated molecular pattern (PAMP) from bacterial membranes into CS became in a promising approach to develop adjuvants, particularly mucosal adjuvants. Therefore, we prepare CS from proteoliposome (PL) obtained from Neisseria meningitidis B (PLCS) and evaluated it for its capability to stimulate the immune system as well as the adjuvant activity.

The vaccine candidate Vibrio cholerae 638 is protective against cholera in healthy volunteers.

Vibrio cholerae 638 is a living candidate cholera vaccine strain attenuated by deletion of the CTXPhi prophage from C7258 (O1, El Tor Ogawa) and by insertion of the Clostridium thermocellum endoglucanase A gene into the hemagglutinin/protease coding sequence. This vaccine candidate was previously found to be well tolerated and immunogenic in volunteers. This article reports a randomized, double-blind, placebo-controlled trial conducted to test short-term protection conferred by 638 against subsequent V.

Novel adjuvant based on a proteoliposome-derived cochleate structure containing native lipopolysaccharide as a pathogen-associated molecular pattern.

Proteoliposomes (PL) from Neisseria meningitidis B have been widely used as a core antigen for antimeningococcal vaccination. PL contain major outer membrane proteins, LPS and phospholipids, and they induce a strong Th1 immune response, but they have low stability in solution. Attending to the need for new vaccine adjuvants, we developed a highly stable cochleate structure (CS) from PL using a technology that allows easy incorporation of new antigens.

Validation of colorimetric assay to detect complement-mediated antibody-dependent bactericidal activity against serogroups B and C Neisseria meningitidis.

Colorimetric serum bactericidal assay (cSBA), based on the addition of glucose and a pH indicator to the culture medium after the bactericidal reaction, was validated. The precision measured as repeatability, intermediated precision, and reproducibility was determined as a percentage in titer coincidence between replicas >/=50. Moreover the use of the freeze-dried complement was evaluated in comparison to the traditionally stored by freezing.

Standardization of Neisseria meningitidis serogroup B colorimetric serum bactericidal assay.

The correlate of protection for serogroup B meningococci is not currently known, but for serogroup C it is believed to be the serum bactericidal assay (SBA). The current SBAs are labor intensive and the variations in protocols among different laboratories make interpretation of results difficult. A colorimetric SBA (cSBA), based on the ability of Neisseria meningitidis serogroup B to consume glucose, leading to acid production, was standardized by using group B strain Cu385-83 as the target.