Adverse Event Following Immunization Monitoring System in Japan.

Although immunization is essential for maintaining public health, adverse events following immunization (AEFI) occur at a certain rate. Therefore, it is extremely important to conduct postimmunization safety monitoring and relief systems to ensure the safe implementation of immunizations for the public. This article summarizes the monitoring system of AEFI and the unique compensation system (so-called relief system) in Japan. In addition, current problems and issues on the AEFI monitoring and relief system will be specified, and immunization-related systems planned to be built in the future in Japan will be introduced.

Antibody Isolation in C. neoformans.

The importance of humoral immunity to fungal infections remains to be elucidated. In cryptococcosis, patients that fail to generate antibodies against antigens of the fungus Cryptococcus neoformans are more susceptible to the disease, demonstrating the importance of these molecules to the antifungal immune response. Historically, antibodies against C. neoformans have been applied in diagnosis, therapeutics, and as important research tools to elucidate fungal biology. Throughout the process of generating monoclonal antibodies (mAbs) from a single B-cell clone and targeting a single epitope, several immunization steps might be required for the detection of responsive antibodies to the antigen of interest in the serum. This complex mixture of antibodies comprises the polyclonal antibodies. To obtain mAbs, B-lymphocytes are harvested (from spleen or peripheral blood) and fused with tumor myeloma cells, to generate hybridomas that are individually cloned and specifically screened for mAb production. In this chapter, we describe all the necessary steps, from the immunization to polyclonal antibody harvesting, hybridoma generation, and mAb production and purification. Additionally, we discuss new cutting-edge approaches for generating interspecies mAbs, such as humanized mAbs, or for similar species in distinct host backgrounds.

Saccharomyces cerevisiae oral immunization in mice using multi-antigen of the African swine fever virus elicits a robust immune response.

African swine fever virus (ASFV) is one of the most complex viruses. ASFV is a serious threat to the global swine industry because no commercial vaccines against this virus are currently available except in Vietnam. Moreover, ASFV is highly stable in the environment and can survive in water, feed, and aerosols for a long time. ASFV is transmitted through the digestive and respiratory tract. Mucosal immunity is the first line of defense against ASFV. Saccharomyces cerevisiae (SC), which has been certified by the U.S. Food and Drug Administration and has a generally recognized as safe status in the food industry, was used for oral immunization in this study. ASFV antigens were effectively expressed in recombinant SC strains with high DNA copy numbers and stable growth though surface display technology and chromosome engineering (δ-integration). The recombinant SC strains containing eight ASFV antigens-KP177R, E183L, E199L, CP204L, E248R, EP402R, B602L, and B646L- induced strong humoral and mucosal immune responses in mice. There was no antigenic competition, and these antigens induced Th1 and Th2 cellular immune responses. Therefore, the oral immunization strategy using recombinant SC strains containing multiple ASFV antigens demonstrate potential for future testing in swine, including challenge studies to evaluate its efficacy as a vaccine against ASFV.

Hybrid response to SARS-CoV-2 and Neisseria meningitidis C after an OMV-adjuvanted immunization in mice and their offspring.

COVID-19, caused by SARS-CoV-2, and meningococcal disease, caused by Neisseria meningitidis, are relevant infectious diseases, preventable through vaccination. Outer membrane vesicles (OMVs), released from Gram-negative bacteria, such as N. meningitidis, present adjuvant characteristics and may confer protection against meningococcal disease. Here, we evaluated in mice the humoral and cellular immune response to different doses of receptor binding domain (RBD) of SARS-CoV-2 adjuvanted by N. meningitidis C:2a:P1.5 OMVs and aluminum hydroxide, as a combined preparation for these pathogens. The immunization induced IgG antibodies of high avidity for RBD and OMVs, besides IgG that recognized the Omicron BA.2 variant of SARS-CoV-2 with intermediary avidity. Cellular immunity showed IFN-γ and IL-4 secretion in response to RBD and OMV stimuli, demonstrating immunologic memory and a mixed Th1/Th2 response. Offspring presented transferred IgG of similar levels and avidity as their mothers. Humoral immunity did not point to the superiority of any RBD dose, but the group immunized with a lower antigenic dose (0.5 µg) had the better cellular response. Overall, OMVs enhanced RBD immunogenicity and conferred an immune response directed to N. meningitidis too.

Determinants of default from completion of child immunization among children aged 15-23 months in Kacha Bira district, Kembata Tembaro zone, South Ethiopia: a case-control study.

Background: Child immunization is crucial to protect children from vaccine-preventable diseases. However, if a child defaults from completing immunization, they are at a greater risk of contracting such diseases. Previous studies have evaluated various factors that contribute to defaulting from immunization, but they did not consider the fear of COVID-19 as a variable. Additionally, there is inconsistency in the factors identified across different areas. This study aimed to examine the determinants of defaulting from child immunization among children aged 15-23 months in Kacha Bira district, Kembata Tembaro zone, South Ethiopia. Methods: A study was conducted using a community-based unmatched case-control design to identify the determinants of child immunization completion. The study included 255 children aged 15-23 months in the Kacha Bira district from 3 May 2022 to 1 June 2022, using a multi-stage sampling technique. Face-to-face interviews of mothers or immediate caretakers of the child were conducted using a mobile device, and the questionnaire was developed using the Kobo Toolbox. The data collected were analyzed using SPSS version 25. Multivariable logistic regression was used to identify the determinants, and the adjusted odds ratio with 95% CI and a p < 0.05 were considered statistical significant. Results: The multivariable logistic regression analysis identified four independent predictors of immunization defaulting. Antenatal care (ANC) follow-up [AOR = 5.40, 95% CI (2.24-13.52)], postponing vaccination schedule [AOR = 2.28, 95% CI: (1.05-4.93)], parity of the mother [AOR = 3.25, 95% CI: (1.45-7.27)], and knowledge of the mother about vaccination [AOR = 6.77, 95% CI: (2.33-19.64)] were determinants of immunization defaulting. Conclusion: In this study, lack of ANC follow-up, postponement of the vaccination schedule, mothers with parity of greater than four, and poor knowledge of the mothers about immunization were identified as determinants of immunization defaulting.

Prediction of incomplete immunization among under-five children in East Africa from recent demographic and health surveys: a machine learning approach.

The World Health Organization as part of the goal of universal vaccination coverage by 2030 for all individuals. The global under-five mortality rate declined from 59% in 1990 to 38% in 2019, due to high immunization coverage. Despite the significant improvements in immunization coverage, about 20 million children were either unvaccinated or had incomplete immunization, making them more susceptible to mortality and morbidity. This study aimed to identify predictors of incomplete vaccination among children under-5 years in East Africa. An analysis of secondary data from six east African countries using Demographic and Health Survey dataset from 2016 to the recent 2021 was performed. A total weighted sample of 27,806 children aged (12-35) months was included in this study. Data were extracted using STATA version 17 statistical software and imported to a Jupyter notebook for further analysis. A supervised machine learning algorithm was implemented using different classification models. All analysis and calculations were performed using Python 3 programming language in Jupyter Notebook using imblearn, sklearn, XGBoost, and shap packages. XGBoost classifier demonstrated the best performance with accuracy (79.01%), recall (89.88%), F1-score (81.10%), precision (73.89%), and AUC 86%. Predictors of incomplete immunization are identified using XGBoost models with help of Shapely additive eXplanation. This study revealed that the number of living children during birth, antenatal care follow-up, maternal age, place of delivery, birth order, preceding birth interval and mothers' occupation were the top predicting factors of incomplete immunization. Thus, family planning programs should prioritize the number of living children during birth and the preceding birth interval by enhancing maternal education. In conclusion promoting institutional delivery and increasing the number of antenatal care follow-ups by more than fourfold is encouraged.

Outer membrane vesicles generated by an exogenous bacteriophage lysin and protection against Acinetobacter baumannii infection.

BACKGROUND: The outer membrane vesicles (OMVs) produced by Gram-negative bacteria can modulate the immune system and have great potentials for bacterial vaccine development. RESULTS: A highly active Acinetobacter baumannii phage lysin, LysP53, can stimulate the production of OMVs after interacting with A. baumannii, Escherichia coli, and Salmonella. The OMVs prepared by the lysin (LOMVs) from A. baumannii showed better homogeneity, higher protein yield, lower endotoxin content, and lower cytotoxicity compared to the naturally produced OMVs (nOMVs). The LOMVs contain a significantly higher number of cytoplasmic and cytoplasmic membrane proteins but a smaller number of periplasmic and extracellular proteins compared to nOMVs. Intramuscular immunization with either LOMVs or nOMVs three times provided robust protection against A. baumannii infections in both pneumonia and bacteremia mouse models. Intranasal immunization offered good protection in the pneumonia model but weaker protection (20-40%) in the bacteremia model. However, with a single immunization, LOMVs demonstrated better protection than the nOMVs in the pneumonia mouse model. CONCLUSIONS: The novel lysin approach provides a superior choice compared to current methods for OMV production, especially for vaccine development.

Immunization adherence among children with sickle cell disease and sickle cell trait: Results of a population-based study.

INTRODUCTION: Despite the importance of timely vaccine completion for protection from infectious disease, there is limited knowledge of the immunization adherence rates of children with sickle cell disease (SCD). METHODS: This is a retrospective cohort study comparing the immunization rates of children with SCD to those with sickle cell trait between 2008 and 2019 in Georgia. Completion rates for each vaccine and the proportion of children with up-to-date status at 24 and 35 months were calculated and compared between the cohorts. Chi-square tests with odds ratios (OR) for differences and 95% confidence intervals (CIs) were reported on the overall up-to-date rates and rates for individual vaccines at 24 and 35 months for the two cohorts. RESULTS: Children with SCD had higher up-to-date rates than children with sickle cell trait at 24 and 35 months. At 35 months, the overall up-to-date rates (OR = 1.17; 95% CI, 1.04-1.31; p = .004) and the four-dose pneumococcal conjugate vaccine series (OR = 1.36; 95% CI, 1.18-1.57; p < .001) were significantly different between the groups. Both cohorts had the highest completion rates for the hepatitis B series and the lowest rates for the varicella vaccine. Doses of diphtheria, tetanus, and acellular pertussis vaccine; varicella; and pneumococcal conjugate vaccines were most commonly missed by children in both cohorts. CONCLUSIONS: Children with SCD have better immunization coverage than children with sickle cell trait, but there is an opportunity for improvement. Policymakers and healthcare professionals should focus on increasing access to care coordination services among children with SCD to ensure on-time and preventive healthcare services.

Immunization Newsletter, v.46, Special Issue on Brazil, May 2024 

Brazil is a vast country, home to more than 200 million people and with a public, universal and free health system. Over the more than 35 years since its creation, the Unified Health System (SUS) has made significant progress, including achieving high vaccination coverage for a large number of vaccine-preventable diseases. Immunization actions in the country are coordinated by the National Immunization Program (NIP). It is in this context that the Brazilian office of the Pan American Health Organization (PAHO), in support of initiatives by CONASS and CONASEMS, has organized a collection of experiences to be published as a supplement to the PAHO Immunization Bulletin. To this end, in partnership with CONASS and CONASEMS, six successful experiences were selected from the different regions of the country, carried out by municipalities out of approximately nine hundred proposals submitted, and three developed by states out of fifty submitted. When these experiences were selected, they were able to present them at events run by the managers themselves, such as the CONASS Technical Chamber on Surveillance, held in May 2023, and at the XXXVII National Congress of Municipal Health Secretariats - CONASEMS, held in July of the same year. They also presented their reports at the XXV National Immunization Conference, held in September 2023 by the Brazilian Society of Immunizations (SBIm), one of the world's largest events on the subject. The reports you can read now in this Immunization Bulletin were written directly by the professionals who developed the experiences presented here. You can feel in them the vivacity of a robust, creative health system that has been fed, since its creation, by the energy of anonymous people who fight every day to defend every life and guarantee the population universal and comprehensive access to health, recognized in Brazil as a right for all and a duty of the State by the Federal Constitution.

Immunization Newsletter, v.46, n.1, Mar. 2024

The Pan American Health Organization (PAHO) publishes the Immunization Newsletter four times a year in English, French, Portuguese, and Spanish. Its purpose is to facilitate the exchange of ideas and information on immunization programs in the Region of the Americas and beyond. It has been published since 1979 in English and Spanish, with French and Portuguese versions beginning in 2001 and 2019, respectively. The March 2024 issue of the quarterly Immunization Newsletter covers the following topics: Third annual meeting of the Regional Monitoring and Re-verification Commission for Measles, Rubella, and Congenital Rubella Syndrome Elimination; PAHO’s Technical Advisory Group (TAG) on Vaccine-preventable Diseases provides regional recommendations on dengue and respiratory syncytial virus vaccines and issues a statement on the ongoing COVID-19 vaccination efforts; Charting the path forward: reflections on PAHO's Communicable Diseases Elimination Initiative and future directions; Towards the Elimination of Diseases Associated with Human Papillomavirus Infection in the French Caribbean: Implementation of a Mass Vaccination Campaign in Schools Since October 2023; Expanded Immunization Program methodology and performance monitoring tool for the Region of the Americas; Sentinel surveillance of rotavirus in children under 5 years of age in the Region of the Americas; Sentinel surveillance of bacterial pneumonia and meningitis in children under 5 years of age in the Americas; Workshop on the preparation of scientific texts and articles on health in Bogotá, Colombia; Final Classification of Cases in the Region of the Americas, 2023; Immunization information systems and data quality; Virtual self-learning course: Tools for monitoring integrated public health interventions. Vaccination and deworming for soil-transmitted helminth infections; and Strengthening immunization data management.

Boletín de Inmunización, v.46, n.1, Mar. 2024

La Organización Panamericana de la Salud (OPS) publica cuatro veces al año el Boletín de Inmunización en español, francés, inglés y portugués. Su propósito es facilitar el intercambio de ideas e información sobre los programas de inmunización en la Región de las Américas y más allá. Se publica desde 1979 en inglés y español, con versiones en francés y portugués a partir de 2001 y 2019, respectivamente. El número de marzo del 2024 del Boletín de Inmunización abarca los siguientes temas: Tercera reunión anual de la Comisión Regional de Monitoreo y Reverificación de la Eliminación del Sarampión, la Rubéola y el Síndrome de Rubeola Congénita; El Grupo Técnico Asesor de la OPS sobre Enfermedades Prevenibles por Vacunación ofrece recomendaciones sobre las vacunas contra el dengue y el virus respiratorio sincitial a nivel regional y emite una declaración referente a los esfuerzos continuos de vacunación contra la COVID-19; Trazando el camino a seguir: reflexiones sobre la Iniciativa para la Eliminación de Enfermedades Transmisibles de la OPS y orientaciones futuras; Hacia la eliminación de las enfermedades debidas al virus del papiloma humano en el Caribe francés: puesta en marcha de una campaña de vacunación masiva en las escuelas a partir de octubre del 2023; Metodología y herramienta de monitoreo del desempeño del Program Ampliado de Inmunización para la Región de las Américas; Vigilancia centinela de rotavirus en los menores de 5 años en la Región de las Américas; Vigilancia centinela de neumonías y meningitis bacterianas en menores de 5 años de edad en las Américas; Taller de Elaboración de textos y artículos científicos en el ámbito de la salud en Bogotá (Colombia); Clasificación final de casos en la Región de las Américas, 2022; El sistema de información de inmunización y la calidad de los datos; Curso virtual de autoaprendizaje “Herramientas para el monitoreo de intervenciones integradas en salud pública. Vacunación y desparasitación para las geohelmintiasis”; y Fortalecer la gestión de los datos de inmunizaciones.

Appendice. Pour une meilleure immunité : l’approche du parcours de vie pour une longévité en bonne santé

Cette publication est une annexe au document technique "Building better immunity : Une approche du parcours de vie pour une longévité en bonne santé", avec les contributions de plusieurs experts en la matière au sein et en dehors de l'Organisation panaméricaine de la santé (OPS). Cette annexe fournit des exemples d'activités au sein du programme national de vaccination qui peuvent améliorer les taux de couverture et réduire les occasions manquées pour quatre groupes de population : les femmes enceintes, les adolescents, les travailleurs de la santé et les personnes âgées. Ces exemples traduisent les principes et les concepts de l'approche fondée sur le parcours de vie en activités concrètes, qui peuvent être utilisées par les responsables des programmes nationaux de vaccination et par les vaccinateurs, respectivement, pour améliorer les taux de couverture vaccinale. Ces quatre groupes représentent des étapes de la vie pour lesquelles il existe des vaccins très efficaces et qui peuvent grandement influencer leurs capacités sanitaires. L'application des séries primaires, des rappels et des doses de vaccin de rattrapage dans ces groupes est essentielle pour combler les déficits d'immunité émergents. Les activités sont regroupées en huit composantes : (i) gestion et plaidoyer, (ii) équité, (iii) ressources humaines et financement, (iv) organisation et prestation de services, (v) génération de la demande et engagement communautaire, (vi) systèmes d'information, (vii) formation et (viii) évaluation et recherche. Les exemples doivent être évalués, adaptés, mis en œuvre et éventuellement élargis par les États membres pour s'aligner sur les contextes nationaux et locaux. Ce document s'inscrit dans le cadre des efforts déployés par l'OPS pour promouvoir l'application d'une approche de la vaccination fondée sur le parcours de vie dans les pays et territoires des Amériques et pour aider les ministères de la santé à mettre en place des stratégies de santé publique aux niveaux infranational et local afin de préserver la santé et le bien-être des personnes de tous âges.

Apéndice. Lograr una mejor inmunidad: El enfoque del curso de vida para una longevidad saludable

Esta publicación es un apéndice del documento técnico "Lograr una mejor inmunidad: el enfoque de curso de vida para una longevidad saludable", con las contribuciones de varios expertos en la materia dentro y fuera de la Organización Panamericana de la Salud (OPS). Este apéndice proporciona ejemplos de actividades dentro del programa nacional de inmunización que pueden mejorar las tasas de cobertura y reducir las oportunidades perdidas para cuatro grupos de población: mujeres embarazadas, adolescentes, trabajadores sanitarios y adultos mayores. Estos ejemplos traducen los principios y conceptos del Enfoque del Ciclo Vital en actividades concretas, que pueden ser utilizadas por los gestores de los programas nacionales de inmunización y por los vacunadores, respectivamente, para reforzar las tasas de cobertura de vacunación. Estos cuatro grupos representan etapas de la vida para las que existen vacunas muy eficaces y que pueden influir enormemente en sus capacidades sanitarias. La aplicación de dosis de vacunas de la serie primaria, de refuerzo y de recuperación en estos grupos es fundamental para cerrar las brechas de inmunidad emergentes. Las actividades se agrupan en ocho componentes (i) administración y promoción, (ii) equidad, (iii) recursos humanos y financiación, (iv) organización y prestación de servicios, (v) generación de demanda y participación de la comunidad, (vi) sistemas de información, (vii) formación y (viii) evaluación e investigación. Los ejemplos deben ser evaluados, adaptados, implementados y posiblemente ampliados por los Estados Miembros para alinearlos con los contextos nacionales y locales. Este documento forma parte de los esfuerzos de la OPS para promover la aplicación de un enfoque de inmunización a lo largo de la vida por parte de los países y territorios de las Américas y para apoyar a los Ministerios de Salud a establecer estrategias de salud pública a nivel subnacional y local para salvaguardar la salud y el bienestar de las personas de todas las edades.

Report from the World Health Organization's immunization and vaccines-related implementation research advisory committee (IVIR-AC) meeting, virtual gathering, 26 February-1 March 2024.

The Immunization and Vaccine-related Implementation Research Advisory Committee (IVIR-AC) is the World Health Organization's key standing advisory body to conduct an independent review of research, particularly of transmission and economic modeling analyses that estimate the impact and value of vaccines. From 26th February-1st March 2024, at its first of two semi-annual meetings, IVIR-AC provided feedback and recommendations across four sessions; this report summarizes the proceedings and recommendations from that meeting. Session topics included modeling of the impact and cost-effectiveness of the R21/Matrix-M malaria vaccine, meta-analysis of economic evaluations of vaccines, a global analysis estimating the impact of vaccination over the last 50 years, and modeling the impact of different RTS,S malaria vaccine dose schedules in seasonal settings.

Co-immunization with DNA vaccines encoding yidR and IL-17 augments host immune response against Klebsiella pneumoniae infection in mouse model.

Klebsiella pneumoniae is an important gram-negative bacterium that causes severe respiratory and healthcare-associated infections. Although antibiotic therapy is applied to treat severe infections caused by K. pneumoniae, drug-resistant isolates pose a huge challenge to clinical practices owing to adverse reactions and the mismanagement of antibiotics. Several studies have attempted to develop vaccines against K. pneumoniae, but there are no licensed vaccines available for the control of K. pneumoniae infection. In the current study, we constructed a novel DNA vaccine, pVAX1-YidR, which encodes a highly conserved virulence factor YidR and a recombinant expression plasmid pVAX1-IL-17 encoding Interleukin-17 (IL-17) as a molecular adjuvant. Adaptive immune responses were assessed in immunized mice to compare the immunogenicity of the different vaccine schemes. The results showed that the targeted antigen gene was expressed in HEK293T cells using an immunofluorescence assay. Mice immunized with pVAX1-YidR elicited a high level of antibodies, induced strong cellular immune responses, and protected mice from K. pneumoniae challenge. Notably, co-immunization with pVAX1-YidR and pVAX1-IL-17 significantly augmented host adaptive immune responses and provided better protection against K. pneumoniae infections in vaccinated mice. Our study demonstrates that combined DNA vaccines and molecular adjuvants is a promising strategy to develop efficacious antibacterial vaccines against K. pneumoniae infections.

The immunostimulatory roles of gold nanoparticles in immunization and vaccination against Brucella abortus antigens.

One effective antigen carrier proposed for use in immunization and vaccination is gold nanoparticles. Prior work has shown that gold nanoparticles themselves have adjuvant properties. Currently, gold nanoparticles are used to design new diagnostic tests and vaccines against viral, bacterial, and parasitic infections. We investigated the use of gold nanoparticles as immunomodulators in immunization and vaccination with an antigen isolated from Brucella abortus. Gold nanoparticles with a diameter of 15 nm were synthesized for immunization of animals and were then conjugated to the isolated antigen. The conjugates were used to immunize white BALB/c mice. As a result, high-titer (1:10240) antibodies were produced. The respiratory and proliferative activities of immune cells were increased, as were the serum interleukin concentrations. The minimum antigen amount detected with the produced antibodies was âˆ¼ 0.5 pg. The mice immunized with gold nanoparticles complexed with the B. abortus antigen were more resistant to B. abortus strain 82 than were the mice immunized through other schemes. This fact indicates that animal immunization with this conjugate enhances the effectiveness of the immune response. The results of this study are expected to be used in further work to examine the protective effect of gold nanoparticles complexed with the B. abortus antigen on immunized animals and to develop test systems for diagnosing brucellosis in the laboratory and in the field.

Activates B lymphocytes and enhanced immune response: A promising adjuvant based on PLGA nanoparticle to improve the sensitivity of ZEN monoclonal antibody.

In preparing monoclonal antibodies by hybridoma cell technology, the quality of B lymphocytes used for cell fusion directly affects the sensitivity of monoclonal antibodies. To obtain B-lymphocytes producing high-quality specific antibodies for cell fusion during the immunization phase of the antigen, we prepared a TH2-Cell stimulatory delivery system as a novel adjuvant. Astragalus polysaccharide has a good ability to enhance antigenic immune response, and it was encapsulated in biocompatible materials PLGA as an immunostimulatory factor to form the delivery system (APS-PLGA). The preparation conditions of APSP were optimized using RSM to attain the highest utilization of APS. Immunization against ZEN-BSA antigen using APSP as an adjuvant to obtain B lymphocytes producing ZEN-specific antibodies for cell fusion. As results present, APSP could induce a stronger TH2 immune response through differentiating CD4 T cells and promoting IL-4 and IL-6 cytokines. Moreover, it could slow down the release efficiency of ZEN-BSA and enhance the targeting of ZEN-BSA to lymph nodes in vivo experiments. Ultimately, the sensitivity of mouse serum ZEN-specific antibodies was enhanced upon completion of immunization, indicating a significant upregulation of high-quality B lymphocyte expression. In the preparation of monoclonal antibodies, the proportion of positive wells for the first screening was 60%, and the inhibition rates of the antibodies were all similar (>50%). Then we obtained the ZEN monoclonal antibody with IC50 of 0.049 ng/mL, which was more sensitive than most antibodies prepared under conventional adjuvants. Finally, a TRFIAS strip assay was preliminarily established with a LOD value of 0.246 ng/mL.

Immunization with a low dose of zymosan A confers resistance to depression-like behavior and neuroinflammatory responses in chronically stressed mice.

Stimulation of the innate immune system prior to stress exposure is a possible strategy to prevent depression under stressful conditions. Based on the innate immune system stimulating activities of zymosan A, we hypothesize that zymosan A may prevent the development of chronic stress-induced depression-like behavior. Our results showed that a single injection of zymosan A 1 day before stress exposure at a dose of 2 or 4 mg/kg, but not at a dose of 1 mg/kg, prevented the development of depression-like behaviors in mice treated with chronic social defeat stress (CSDS). The prophylactic effect of a single zymosan A injection (2 mg/kg) on CSDS-induced depression-like behaviors disappeared when the time interval between zymosan A and stress exposure was extended from 1 day or 5 days to 10 days, which was rescued by a second zymosan A injection 10 days after the first zymosan A injection and 4 days (4×, once daily) of zymosan A injections 10 days before stress exposure. Further analysis showed that a single zymosan A injection (2 mg/kg) 1 day before stress exposure could prevent the CSDS-induced increase in pro-inflammatory cytokines in the hippocampus and prefrontal cortex. Inhibition of the innate immune system by pretreatment with minocycline (40 mg/kg) abolished the preventive effect of zymosan A on CSDS-induced depression-like behaviors and CSDS-induced increase in pro-inflammatory cytokines in the brain. These results suggest that activation of the innate immune system triggered by zymosan A prevents the depression-like behaviors and neuroinflammatory responses in the brain induced by chronic stress.