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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.

mmunization 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.

This research aimed to study the effects of reading aloud at the level of reading comprehension in elementary school students. The quantitative approach was assumed with a type of explanatory study under a quasi-experimental design with prebrand-posttest in a single experimental group. The sample was represented by a total of 33 students, after meeting criteria of inclusion and exclusion, they were applied the reading comprehension test of Progressive Linguistic Complexity (CLP), by Alliende, Condemarín, and Milicic, (1991). After the application, the strategy of the reading program in voice was executed in a period of time of 4 months. The analysis of the results was performed with the statistical package SPSS version 22 with the application of non-parametric statistics, since the sample did not present a normal distribution, so the Wilcoxon test was used, with a level of significance of 0.05. The results showed that students after application of the program significantly improved levels literal (p: 000) and inferential (p: 0.014 and p: 0.001). However for the critical textual level (p: 0.485 and p: 0.034) there is no statistical significance. It is concluded that levels of reading comprehension can improve with the intervention of reading aloud at their literal and inferential levels and it is corroborated that as one moves to another level of reading, the complexity is greater and to reach it is required Greater work and time. [ABSTRACT FROM AUTHOR]

The focus of research is the study of learning strategies and academic achievement in students of primary education public institution Policarpa Salavarrieta. As a non-experimental methodology selective ex post-facto design or assumed, because the participants were selected according to their personal characteristics and a relationship between the variables under study were established: learning strategies (VI) and academic performance (VD); picking a purposive sample of 60 Grade 5 students who responded to the application of the ACRA Scale ROMÁN AND GALLEGO (1994). The analyzes were descriptive of the main study variables and linear correlations between learning strategies and academic performance. The results showed statistically significant correlations between different scales of ACRA Test being all positive, just as it can be seen that subjects such as Spanish Language and Natural Sciences have a strong association. Finally it was concluded that the association between the variables of learning strategies and academic performance, so it can be stated that the appropriate use of learning strategies depend on the scope of academic performance. [ABSTRACT FROM AUTHOR]

The total and specific IgE response to Angiostrongylus cantonensis infection was evaluated according to host permissiveness. Total IgE levels measured by a double antibody radioimmunoassay (RIA) increased slowly in the permissive host (the rat), reaching a maximum between 4 and 8 weeks after infection. This maximum was earlier but significantly lower in the non-permissive host (the guinea pig). IgE antibodies specific for adult worms or L1 or L3 larvae of A. cantonensis were measured by a radioallergosorbent test (RAST). In the case of adult worms and L1 antigens, specific IgE antibody levels showed large variations in relation to the duration of infection in rats. In contrast to total IgE levels, the specific IgE response to L3 larvae was lower in rats than in guinea pigs in both the serum and cerebrospinal fluid (CSF). These results suggest variations in the total vs specific IgE response according to host permissiveness or non-permissiveness to A. cantonensis infection. These results are discussed in the context of the possible participation of IgE antibodies in immune defence. [ABSTRACT FROM AUTHOR]

VA-MENGOC-BC™ is an outer membrane protein based vaccine of serogroup B of Neisseria meningitidis. It also contains the serogroup C polysaccharide (PsC) which is non-covalently incorporated. We recently demonstrated the participation of other mechanisms possibly involved in it's protection which include, first a characteristic Th1 response induced by this vaccine in young adults and toddler demonstrated at different levels: functional (presence of delayed-type hypersensitivity, opsonophagocytic and bactericidal activities and not immediate anaphylaxis nor passive cutaneous anaphylaxis); class and subclasses (IgG and IgG1); molecular (induction of IL2 and γIFN mRNA and not IL4 nor IL5 mRNA); posttranscriptional (production of IL2 and γIFN and not IL4 nor IL5 in supernatant of restimulated peripheral cells); and the biological activity of γIFN produced. Second, a typical anti-PsC IgG secondary response was induced in toddler which demonstrated that this vaccine overcome the absence of response of the PsC, a thymus independent (TI) antigens. As was expected, the unconjugated polysaccharide vaccine stimulated IgG2 antibody subclass in agreement with previous reports. The subclass response is changed by VA-MENGOC-BC™ to IgG4 and IgG3. Third, the priming induced by PsC not induced hyporesponsiveness after a booster dose. In conclusion, we showed: the induction of Th1 pattern at different levels, the influence of this pattern over the response of a TI antigen in toddler and the not induction of hyporesponsiveness by PsC antigens after a booster dose. [ABSTRACT FROM AUTHOR]

The role of neutrophils (PMN) as effector cells against bacterial infection and the production of cytokines in response to polysaccharide (LPS) are well documented. However, no conclusive data of the importance of PMN as effector cell in Neisseria infection and no data about the possible role of PMN in the afferent arm of the immune response were reported. Therefore, we used a neutropenic rat model and infected theme with N. meningitidis B. The neutropenic animals showed a 100% of mortality in less than 12 h and 0% in control. The bacteriolytical activity of co-cultures of human PMN and N. meningitidis B was demonstrated, which was increased with LPS and γIFN. In the afferent arm, the presence of high concentration of PMN around the site of immunization with anti-N. meningitidis B vaccine, VA-MENGOC-BC™, in hystopathologic studies was observed. In addition, the outer membrane vesicles (OMV) from N. meningitidis B stimulated PMN and produced pro-inflammatory cytokines and chemokines including TNFα, IL-1β, IL-8, MIP-1α/β which are increased by γIFN. IP-10 was also produced by OMV+γIFN. IL-10, a regulatory cytokine, potently inhibited TNFα, IL-1β, IL-8, and MIP-1α/β production triggered by OMV. Finally, a neutralizing anti-TNFα MAb did not influence the release of IL-8 and MIP-1β induced by OMV, therefore excluding a role for endogenous TNFα in mediating the induction of chemokine release by OMV. In contrast, the ability of LPS from N. meningitidis B to induce the production of IL-8 and MIP-1α was significantly inhibited by anti-TNFα MAb. In conclusion, our results establish the role of PMN as essential effector cells and that in response to OMV, PMN produce a pro-inflammatory profile of cytokines and chemokines which may not only play a role in the pathogenesis of meningitis, but may also contribute to the development of protective immunity to serogroup B meningococci. [ABSTRACT FROM AUTHOR]

T cell independent antigens do not require T cell help to induce immune response, and are not capable to induce immunological memory. To overcome the problem associated with the thyme-independent (TI) nature of polysaccharides (PS) antigens, vaccines strategies have focused on converting the TI-2 immune response to a thyme-dependent (TD) immune response. Conjugate vaccines convert PS to a TD antigen and increased its immunogenicity. Mucosal vaccination is the only effective mean to induce secretory immunity at the site of infection and at distant sites. The use of mucosal adjuvants is a promising tool to further improve the immune response. VA-MENGOC-BC® is the Cuban vaccine that contains outer membrane vesicles (Proteoliposome, PL) and polysaccharide from N. meningitidis serogroups B and C (PSC). AFCol, a microparticle derived from PL with adjuvant function (AFPL1) had demonstrated be a potent mucosal adjuvant. In this work, we evaluated the response induce by VA-MENGOC-BC® in infants and toddlers. The vaccine does not induce hyporesponsiveness to future challenge. High anti PSC IgG were seen following the administration of two doses in infant and toddler. The anti PSC IgM response was maintained and the subclasses pattern induced was IgG4>lgG3>lgGl. By other side, we demonstrated that 3 intranasal (i.n) doses of PSC with AFCol in mice promote higher specific anti PSC IgA responses (p<0.001) in saliva and vaginal wash. The specific anti PSC IgG response (p<0.05) was superior than i.n PSC, but not different to i.m VA-MENGOC-BC®. The long-time mucosal and systemic memory responses were evaluated, after the booster immunization with PSC 70 days later of the last immunization. These results suggest that non-covalent conjugation of PSC to AFPL1 in VA-MENGOC-BC®, is immunogenic, primes for memory and induce a preferential and potent Th1 response in infants and toddlers against PSC. Also, our findings show that AFCol are capable to act as a potent mucosal adjuvant inducing mucosal, systemic, and memory responses in mice without need of conjugation against PSC and redirect the response to a Th1 pattern. [ABSTRACT FROM AUTHOR]

Neisseria gonorrhoeae is the etiologic agent of the sexually transmitted diseases Gonorrhoea. Gonorrhoea appears in asymptomatic or otherwise, symptomatic with uncomplicated or complicated outcome mainly in women. Although treatable, increased antibiotic-resistant of N. gonorrhoeae strains were reported and no vaccine is currently available. N. meningitidis is another human restricted bacterium transmitted through oropharyngeal mucosa with some degree of systemic IgG crossrecognition with N. gonorrhoeae. We have recently found that nasal immunization of mice with AFCol induces anti N. meningitidis immune responses in the serum and female genital tract with the ability to recognize N. gonorrhoeae antigens. Here, we extended these results to mucosal immune response in mice and humans and also analysed the epidemiological Cuban data for both N. meningitidis and N. gonorrhoeae prevalence in relationship with meningococcal interventions. The intramuscular (I.M) application of VA-MENGOC-BC® human vaccine, AFPL1 in Alum, or AFCol induced specific systemic IgG antibody response in Balb/c mice. VA-MENGOC-BCe and AFCol induced comparable levels of specific igG antibody responses, but they were higher than that induced by AFPL1 in Alum. Neither VA-MENGOC-BC® nor AFPL1 or AFCol applied via I.M route induced saliva specific IgA antibody. Nevertheless, intranasal (I.N) application of AFPL1 and AFCol induced systemic specific IgG and mucosal specific IgA in mice, although higher in AFCol than AFPL1 immunized mice. In order to test the possible boost effect of mucosai immunization in I.M immunization setting with VA-MENGOC-BC®, mice were immunized with 2 I.M doses of VA-MENGOC-BC® followed by a I.N booster dose with AFPL1 or AFCol. These mice developed saliva specific IgA antibody comparable to that of mice immunized 3 I.N. These results indicate that heterogenous systemic prime-mucosai boost immunization regime using VA-MENGOC-BC® and AFPL1 or AFCol can induce a potent systemic and mucosal immune response. Lastly, we analyzed the N. gonorrhoeae incidence results since 70's in Cuba and found that the N. gonorrhoeae incidence decreased after introduction of meningococcal BC vaccine. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The authors highlight the results of their study on the effects of meningococcal vaccine VA-MENGOC-BC on the prevalence of Neisseria meningitidis gonorrhoeae in Cuba from 1979 to 1999. Cases of gonorrhoeae caused by serogroups C and A have reduced after vaccination of people below 20 years old. A decrease in cases was noted immediately after the serogroups BC vaccination of people three months to 19 years old from December 1988 to December 1990. Its administration in infants three and five months old since 1991 has reduced mortality by more than 98%.

Malaria is the more important tropical disease being the third transmissible disease killer. The incidence is more than 500 x 106 of clinical cases in 100 countries, with more than 1.1 x 106 death, mainly in children under 5 year old and in pregnant women. During pregnancy the infected erythrocytes are marginalized in the placenta. We hypothesized that during pregnancy the occurrence of necrosis permits the pass of malaria merozoites/antigens that induce tolerance; which could explain the absence or altered response of new born and their high mortality by anaemia. Rats were infected Plasmodium berghei NK65 at -7, -5 or -3 days of delivery corresponding to early, middle, or late stage of gestation, respectively. This schedule was performed in young or adults rats, corresponding to 7±2 or 11 weeks of born, respectively. The duration of gestation was prolonged during middle and late infection mainly in young pregnant infected rats. Seventy five and 12.3% of stillborns in young or adult late infected pregnant rats, respectively were observed. In addition, 43% of new born mortality in adult late infected pregnant rats was observed. Low birth weight was only observed in young late infected pregnant rat. Maternal mortality was observed in 41,7% of young late infected pregnant rat. The 100% and 50% of new born from infected mother have congenital malaria and anaemia, respectively. Formulation containing Finlay Adjuvant and malaria antigens by intramuscular or nasal routes induce Th1 immune response. This formulations work in new born mice. Several human malaria signs were reproducing in pregnant rat model. Go deeper in tolerance induction is the new step. [ABSTRACT FROM AUTHOR]

Vaccination is considered to be the most cost-effective strategy for controlling infectious diseases. Epidemiologically targeted implementation of vaccines has diminished morbidity and mortality from many infectious diseases that previously were scourges and economic burdens, in spite of the great successes with current vaccines, many infections diseases are still leading killers, mainly due to they inadequate coverage. Several factors have been largely responsible to attain immunization coverage and have been appointed as the main problems of current vaccines. Therefore, we develop the Single Time Vaccination Strategy (SinTimVaS) where a mucosal priming and parenteral boost are given simultaneosly.To evaluate the systemic and mucosal immune response against Ovalbumin, Seroalbumin, Tetanus Toxoid, and Proteoliposome induced by SinTimVaS using Finlay adjuvants, AFCol and AFPL1. One Intranasal dose of AFCol and one Intramuscular dose of AFPL1 administrated in SinTimVaS, induce specific systemic and mucosal immune response against all antigens tested. SinTimVaS is not restricted to the combination of Intranasal and Intramuscular routes. It also functions by combinations of Intragastric or Sublingual, and subcutaneous routes. In addition, SinTimVaS also functions with other mucosal adjuvant like Cholera Toxin. Lastly, SinTimVaS induces regional and distal mucosal response. SinTimVaS was effective against all antigens tested which could increases vaccination coverage, compliance, and induces systemic and mucosal immune responses. [ABSTRACT FROM AUTHOR]

The use of new adjuvants in vaccine formulations is a subject of current research. Only few parenteral adjuvants have been licensed. We develop a mucosal and parenteral adjuvant entitled AFCol (Adjuvant Finlay Cochleate 1) using dialysis procedures at lab scale. In order to increase the production process, we used a crossflow system (CFS) that allows easy scale up to obtain large batches in an aseptic environment. The aim of this work is to produce AFCol at pilot scale conserving adjuvanticity. As results the AFCol was successful produced by tangential filtration to scale pilot. It passes preclinical toxicity studies and preliminary stability. The nasal immunogenicity evaluated in Balb/c mice induced specific saliva IgA and serum IgG. The induction of Th-1 response was demonstrated by the induction of IgG2a, IFNγ, and not IL-5. The self adjuvant action as well as against co-administered antigens were similar to Lab scale lots. The AFCol obtained at pilot scale conserve the mean physicchemical and immunological characteristics for 2 years with no preclinical toxicity. [ABSTRACT FROM AUTHOR]

Neonates have a poorly developed immune system. Hence safe and powerful adjuvants may be used to enhance the immune response in early life. Neisseria meningitidis B proteoliposome (AFPL1 when it is used as adjuvant) and its derivative-Cochleate (AFCol) contain immunopotentiating and immunomodulating properties and delivery system capacities required for a good adjuvant. AFPL1 in addition to its use in meningococcal vaccination has ended the preclinical stage in an allergy vaccine and adjuvant properties of AFCol have also been previously demonstrated using model antigens, including egg albumin (OVA) and Plasmodium falciparum recombinant merozoite surface proteins (MSP) 4 and 5. In the current study, the ability of AFPL1 and AFCol adjuvants to enhance the immune response against OVA and MSP1 from R falciparum in neonatal mice was tested. One week old mice were immunized with the incorporated antigen into de adjuvants (AFPL1-OVA and AFCol-OVA) or coadministrated with those adjuvants (AFPL1 +OVA, AFCol +OVA and AFCol +MSPt) by intranasal route (i.n), 3 times, 7 days apart and anti-specific antigens systemic and mucosal antibody responses were measured by ELISA. AFCol +MSP1 was also administered intramuscularly (i.m) with two doses, 14 days apart. AFPL1 and AFCol induced significant levels of anti OVA IgG antibodies in comparison with controls. It was higher when OVA were delivered incorporated into the adjuvant. Anti OVA secretory IgA in saliva were only found in AFPL1-OVA and AFCol-OVA groups. The addition of AFCol as adjuvant enhanced MSPl-specific IgG responses following either i.n or i.m MSPI. Although it was not achieved the levels obtained i.n of adults mice with similar immunization, these results suggest that the use of AFCol and AFPL1 as adjuvant may be able to circumvent some of the limitations of neonatal antibody response in early life. [ABSTRACT FROM AUTHOR]

The Adjuvant Finlay Cochleate 2 (AFCo2) is a microtubular structure derived from Vibrio cholerae O1 proteoliposome (PL). It contains multiple antigens and immunepotentiator molecules like MSHA pilus, OmpU porin and lypopolisaccharide (LPS). Intranasal (IN) administration of AFCo2 (100 ug) induces high systemic and mucosal immune response comparable with attenuated 638 vaccine candidate on BALB/c mice and was used as positive control. The aim of this work is to evaluate the effect of dose and pH gastric attenuation on mucosal and systemic immune response induced by AFCo2 intragastric (IG) immunization. AFCo2 was obtained by rotary dialysis method and characterized using SDS/PAGE, Western Blotting (monoclonal antibodies from Finlay Institute) and light microscopy. BALB/c mice were IG immunized with 100 ug or 200 ug of AFCo2 with or without sodium bicarbonate using a three doses one week apart schedule. Saliva and faeces samples were collected at seven and fourteen days after the last dose, respectively. Specific (anti PL) systemic and mucosal immune responses were evaluated using ELISA procedures to detect IgG (sera) or IgA (saliva and faeces) antibodies. Additionaly, vibriocidal activity was determined in sera. AFCo2 structures sized~16.45 um were obtained and the main antigens/immunepotentiator molecules were not affected during transformation. Besides 200 ug of AFCo2 immunized by IG induced better specific mucosal and systemic immune responses than 100 ug and finally pH neutralization did not affect the specific immune responses induced. Overall, AFCo2 was obtained by dialysis rotary method, the IG immunization required higher dose than IN route to induced comparable specific immune responses and Gastric pH attenuation using AFCo2 is not required to induce highly immune responses. [ABSTRACT FROM AUTHOR]

The most attractive route of vaccination is mucosal immunisation, because of its high patient compliance, ease of administration, and applicability to mass vaccination. This strategy constitutes a challenge for vaccines development, because it is necessary the presence of efficient and safety adjuvants. The AFCol have demonstrated be a potent nasal adjuvant. To evaluate the systemic and mucosal immune response against Tetanus Toxoid (TT) using the Finlay adjuvant, AFCol and the mucosal and systemic short time and long time memory responses induced against 11. This work showed that intranasal immunisation (i.n) of AFCol coadministrated with TT in 3 doses, seven days apart significant increase the anti TT IgA response in saliva and vaginal wash (p<0.05 and p<0.001, respectively). The i.n immunisation also induced statistics significant specific IgG response (p<0.001). Short time systemic memory response, by a prime-boost schedule, and long time mucosal and systemic memory responses, using the classic schedule of 3 doses and 90 days later a boost immunisation with TT alone, were higher than primary responses. These results demonstrate that AFCol is a potent mucosal adjuvant to TT and it is capable to induce memory responses. [ABSTRACT FROM AUTHOR]

The Cuban outer membrane vesicles (OMV) vaccine against Neisseria meningitidis, VA-MENGOC-BC™ induces a preferential cellular (Th1) pattern in mice and human. It contains OMV and polysaccharide C (PsC) from B and C serogroups at equal concentrations, respectively. Traditionally, relative high concentrations of OMV and PsC and several weeks between each two doses for mice immunisation were used. Nevertheless, the better time and interval for each antigen dose was never been addressed. Therefore, we compared doses of: 25, 12.5, 6.25, 3.125, 1.56, and 0.7 per mouse and intervals of: 7, 14, 21, 28, 35, 42, 56, and 63 days between each dose. The anti-OMV and anti-PsC IgG class and IgG2a and IgG1 subclasses were determined by ELISA. The production of gamma-IFN from spleen cells restimulated in vitro with OMV and the delayed-type hypersensitivity (DTH) were measured. All schedules (doses and intervals) showed high anti-OMV IgG responses although the anti-PsC IgG was more dependent of the schedule used. DTH was higher when lower doses and intervals times were applied although higher doses require longer intervals period for good DTH induction. The anti-OMV and PsC IgG2a subclass were well induced in all schedules. The gamma-IFN production was demonstrated was demonstrated in all schedules but it was higher with concentration of 3.125 or 6.25 µg. In summary, in preclinical studies we can used short intervals between doses and preferentially low concentrations, but the response induced by PsC seen to need more interval between dose in agreement with the reported more permanence of this antigen in inductive sites [ABSTRACT FROM AUTHOR]

The U937 (human histiocytic) and J774 (murine macrophage) cell lines are important tools for adjuvant screening. The U937 produces IL-12, while J774 produce Nitric Oxide (NO). The production of these molecules could be used for the screening of the stimulation capabilities of different adyuvant preparations. IL-12 and NO are mediators of proinflammatory immune responses and they are related with the activation of type 1 T helper (Th1) cells. The outcome and severity of some diseases is directly related to the prevalence of activated Th1 or Th2 cells. This balance is crucial for the development of successful vaccines and adyuvant formulations although this point of view is often dismissed. IL-12 produced by antigen presenting cells, is the main cytokine related with the induction of Th1 pattern. Nitric Oxide (NO) is a molecules which could be also associated to this pattern. For that reason we use U937 and J774 cell lines to test the production of IL-12 or NO, respectively, by the stimulation with different adjuvants. IL-12 was measured by ELISA and NO was determined by Griess reaction. Both molecules were induced and the kinetics were found. The induction of both molecules were observed with the adjuvant alone. [ABSTRACT FROM AUTHOR]

The outer-membrane-derived proteoliposome (PL) of Neisseria meningitidis 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 Dermatophagoides siboney 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 0.4 µg Der s2 allergen, PL and Alum, at 7 days intervals, by subcutaneous route. Furthermore, mice were subjected to an allergen aerosol challenge for 6 consecutive days. Serum IgE, IgG1, and IgG2a allergen-specific antibodies were assessed by ELISA. Cytokine levels in supernatants of D. siboney stimulated lymphocyte cultures and in bronchoalveolar lavage (BAL) were measured by ELISA. Lung tissues were subjected to histological examination. The vaccine prevented the development of both, systemic (IgE) and local allergic responses (featuring lower IL-4, and IL-5 levels in BAL) upon allergen exposure by the inhalant route. Histological examination showed also a diminished allergic inflammatory response in the lungs. After the allergen challenge, cytokine levels in stimulated lymphocyte cultures showed lower values of IL-13 and augmented IFN-γ and IL-10. The vaccine induced a mixed IgG2a/IgG1 antibody response; although only IgG2a was PL-dependent. Both, IgG1/IgE and IgG2a/IgE ratios, showed significantly greater values in vaccinated mice. The findings support a preventative anti-allergic effect associated with the induction of a Th1-like IFN-γ/IL-10 response. IgG1/IgE and IgG2a/IgE ratios could be useful biomarkers for translation into clinical trials., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 Ramirez, Torralba, Bourg, Lastre, Perez, Jacquet and Labrada.)

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. Contradictorily, few vaccines are of single dose and even less of mucosal administration. However, more common infections occur via mucosa, where secretory immunoglobulin A plays an essential role. As an alternative, we proposed a novel protocol of vaccination called Single Time Vaccination Strategy (SinTimVaS) by immunizing 2 priming doses at the same time: one by mucosal route and the other by parenteral route. Here, the mucosal and systemic responses induced by Finlay adjuvants (AF Proteoliposome 1 and AF Cochleate 1) implementing SinTimVaS in BALB/c mice were evaluated. One intranasal dose of AF Cochleate 1 and an intramuscular dose of AF Proteoliposome 1 adsorbed onto aluminum hydroxide, with bovine serum albumin or tetanus toxoid as model antigens, administrated at the same time, induced potent specific mucosal and systemic immune responses. Also, we demonstrated that SinTimVaS using other mucosal routes like oral and sublingual, in combination with the subcutaneous route elicits immune responses. SinTimVaS, as a new immunization strategy, could increase vaccination coverage and reduce time-cost vaccines campaigns, adding the benefits of immune response in mucosa.

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. The aim of this work was to explore the efficacy of AFCo1 or AFPL1, as mucosal adjuvants to stimulate cell immunity and memory responses against Vi polysaccharide antigen of Salmonella typhi (PsVi). Mice immunized with 3 intranasal doses exhibited high levels of PsVi-specific IgG (p<0.05), IgG2a and IgG2c subclasses. Also, an amplified recall response after a booster immunization with a plain polysaccharide vaccine was induced. Avidities index were higher in mice immunized with adjuvanted formulations at different chaotropic concentrations. Furthermore, IL-12 and IFN-γ levels in nasally vaccinated mice with both adjuvants were induced. Moreover, priming with 3 doses followed by booster immunization with VaxTyVi(®) resulted in high levels of anti-Vi specific IgG, IgG subclasses and antibody avidity. Long lived plasma cells in bone marrow, memory B cells and long-term memory T cells after booster dose were induced. The combined formulation of Vi polysaccharide with mucosal adjuvants provides an improved immunogenicity, in particular with regard to cellular responses and long lasting cells responses., (Copyright © 2014 Elsevier Ltd. All rights reserved.)