Background: Overall, there are over 30 different sexually transmitted infections with Neisseria gonorrhoeae being the third most frequent with a reported 78 million cases per year. Gonococcal infection causes genital inflammation, which can be a risk factor for others sexually transmitted infections, particularly human immunodeficiency virus. Gonorrhea is a treatable disease, but recently an increase in antibiotic resistance has been of concern. There are currently no vaccines available. However, parenteral vaccination with anti N. meningitidis serogroup B vaccine has been reported to decrease the incidence of gonococcal burden in New Zealand and in Cuba despite the fact that parenteral vaccination is not deemed to induce mucosal IgA. Here we explore possible mechanisms of protection against gonococcal infection through parenteral meningococcal B vaccination. Methods: Ninety-two serum, saliva and oropharyngeal swabs samples of young adults (healthy and Neisseria carriers) of the internal higher school were obtained. They have been vaccinated with VA-MENGOC-BC (MBV) during their infancy and boosted with a third dose during this study. Serum and saliva samples were analyzed by ELISA and Western blot to measured IgG and IgA antibodies against N. meningitidis and N. gonorrhoeae antigens. N. meningitidis carriers were determined by standard microbiologic test. In addition, we reviewed epidemiologic data for N. meningitidis and N. gonorrhoeae infections in Cuba. Results: Epidemiologic data show the influence of MBV over gonorrhea incidence suggesting to be dependent of sexual arrival age of vaccines but not over syphilis. Laboratorial data permit the detection of 70 and 22 noncarriers and carriers of N. meningitidis, respectively. Serum anti-MBV antigens (PL) responses were boosted by a third dose and were independent of carriage stages, but saliva anti-PL IgA responses were only present and were significant induced in carriers subjects. Carriers boosted with a third dose of MBV induced similar antigonococcal and -PL saliva IgA and serum IgG responses; meanwhile, serum antigonococcal IgG was significantly lower. In saliva, at least 2 gonococcal antigens were identified by Western blot. Finally, gonococcal-specific mucosal IgA antibody responses, in addition to the serum IgG antibodies, might contributed to the reduction of the incidence of N. gonorrhoeae. We hypothesize that this might have contributed to the observed reductions of the incidence of N. gonorrhoeae. Conclusion: These results suggest a mechanism for the influence of a Proteoliposome-based meningococcal BC vaccine on gonococcal incidence.

Background/Objectives: The ongoing evolution of SARS-CoV-2 has highlighted the limitations of parenteral vaccines in preventing viral transmission, largely due to their failure to elicit robust mucosal immunity. Methods: Here, we evaluated an intranasal (IN) vaccine formulation consisting of recombinant receptor-binding domain (RBD) adsorbed onto human probiotic Bacillus subtilis DG101 spores. Results: In BALB/c mice, IN spore-RBD immunization induced strong systemic and mucosal humoral responses, including elevated specific IgG, IgM, and IgA levels in serum, bronchoalveolar lavage fluid (BALF), nasal-associated lymphoid tissue (NALT), and saliva. It further promoted mucosal B cell and T cell memory, along with a Th1/Tc1-skewed T cell response, characterized by increased IFN-γ-expressing CD4⁺ and CD8⁺ T cells in the lungs. Conclusions: All in all, these findings highlight the potential of intranasal vaccines adjuvanted with probiotic B. subtilis spores in inducing sterilizing immunity and limiting SARS-CoV-2 transmission.

Background. Mucosal vaccination offers the possibility of establishing immune protection directly at portals of pathogen entry, but its development remains constrained by biological, technological, and implementation barriers. Objective. To integrate the major challenges limiting mucosal vaccination within a common framework and examine emerging strategies capable of addressing several of these barriers simultaneously. Results and Discussion. We consider six interconnected challenges: incomplete recognition of the determinant role of adjuvants; scarcity of safe and accessible mucosal adjuvants; the need to overcome mucosal tolerance while preserving tissue homeostasis; dependence on coldchain logistics; reliance on multidose immunization schedules to achieve protective immunity; and limited breadth of vaccine-induced cross-reactive protection. To better capture the complexity of modern vaccine platforms, we discuss expand adjuvant activity as exogenous, self-adjuvanting, or endogenous according to the origin of the immunostimulatory signal. Particular emphasis is placed on proteoliposome- and cochleate-based systems and probiotic Bacillus subtilis spores as multifunctional platforms combining antigen delivery with intrinsic immunostimulatory properties. Preclinical studies support their capacity to induce systemic IgG, mucosal secretory IgA, cellular responses, and memory response, while their heat resistance may facilitate the development of more thermostable formulations. We also discuss the Single Time Vaccination Strategy as an approach to combined-route immunization and consider glycans and other microbial structures as potential contributors to antigen-specific and cross-reactive mucosal responses. Conclusions. Future mucosal vaccine development should consider adjuvants as tools for coordinated antigen delivery, innate sensing, immune programming with polarization activity, and mucosal memory rather than solely as immune potentiators and delivery system. Probiotic spores, cochleates, and combined-route strategies provide promising examples of this integrated approach, although their translational value will require rigorous demonstration of formulation stability, mechanisms of action, safety, protective breadth, and clinical efficacy.