INTRODUCTION: This review aims to provide evidence-based recommendations for an enhanced primary series (third dose) coronavirus disease 2019 (COVID-19) vaccination in people with rheumatic diseases (PRDs) in the local and regional context. METHODS: Literature reviews were performed regarding the necessity, efficacy, safety and strategies for enhanced primary series COVID-19 vaccination in PRDs. Recommendations were developed based on evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Evidence was synthesised by eight working group members, and the consensus was achieved by a Delphi method with nine members of an expert task force panel. RESULTS: Two graded recommendations and one ungraded position statement were developed. PRDs have impaired immunogenicity from the COVID-19 vaccine and are at an increased risk of postvaccine breakthrough severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and poor clinical outcomes, compared to the general population. We strongly recommend that PRDs on immunomodulatory drugs be offered a third dose of the messenger RNA (mRNA) vaccine as part of an enhanced primary series, after the standard two-dose regimen. We conditionally recommend that the third dose of mRNA vaccine against SARS-CoV-2 be given at least 4 weeks after the second dose or as soon as possible thereafter. There is insufficient data to inform whether the third mRNA vaccine should be homologous or heterologous in PRDs. CONCLUSION These recommendations that were developed through evidence synthesis and formal consensus process provide guidance for an enhanced primary series COVID-19 vaccination in PRDs.
Humans ; COVID-19/prevention & control* ; COVID-19 Vaccines/administration & dosage* ; Rheumatic Diseases/immunology* ; Singapore ; SARS-CoV-2 ; Vaccination/methods* ; Delphi Technique ; Immunization, Secondary

Objective The prevalence of drug-resistant Mycobacterium tuberculosis (Mtb) strains is exacerbating the global burden of tuberculosis (TB), highlighting the urgent need for new treatment strategies for TB. Methods The recombinant adenovirus vaccine expressing cyclic di-adenosine monophosphate (c-di-AMP) phosphodiesterase B (CnpB) (rAd-CnpB), was administered to normal mice via mucosal immunization, either alone or in combination with drug therapy, to treat Mtb respiratory infections in mice.Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of antibodies in serum and bronchoalveolar lavage fluid (BALF). Real-time quantitative PCR was performed to assess the transcription levels of cytokines interferon γ(IFN-γ) and interleukin 10(IL-10) in mouse lungs. Flow cytometry was used to determine the proportions of CD4⁺ and CD8⁺ T cell subsets in the lungs and spleens. ELISA was employed to measure the levels of cytokines IFN-γ, IL-2, IL-10, inflammatory factors IL-6, and tumor necrosis factor α (TNF-α) secreted by spleen cells following antigen stimulation. The bacteria loads in the lungs and spleens of Mtb-infected mice were enumerated by plate counting methods. Resluts Intranasal immunization with rAd-CnpB induced high titers of IgG in mouse serum and the production of IgG and IgA in BALF, along with alterations in T lymphocyte subsets in the lungs and spleens. Administration of rAd-CnpB, either alone or in combination with drugs, to Mtb-infected mice significantly increased serum IgG levels as well as IgA and IgG levels in BALF. rAd-CnpB immunization promoted the secretion of CnpB-specific cytokines and inflammatory factors by splenocytes in Mtb-infected mice. However, rAd-CnpB immunotherapy, either alone or combined with drugs, did not significantly affect the bacterial loads in the lungs and spleens of mice with Mtb respiratory infections. Conclusion Mucosal immunization with rAd-CnpB induced significant mucosal, humoral and cellular immune responses in mice, and significantly enhanced CnpB-specific cellular immune responses in Mtb-infected mice.
Animals ; Adenoviridae/immunology* ; Mycobacterium tuberculosis/genetics* ; Mice ; Female ; Phosphoric Diester Hydrolases/genetics* ; Tuberculosis Vaccines/administration & dosage* ; Tuberculosis/prevention & control* ; Mice, Inbred BALB C ; Cytokines ; Lung/microbiology* ; Immunization ; Bronchoalveolar Lavage Fluid/immunology* ; Immunity, Mucosal

In recent years, the incidence rate of pertussis in China has been steadily increasing, presenting an increasingly severe challenge for disease prevention and control. To strengthen the immune barrier in the population and effectively curb the spread of pertussis, National Disease Control and Prevention Administration of China and other relevant authorities optimized the immunization procedure for diphtheria-tetanus-pertussis vaccine, with the new procedure implemented in 2025. This adjustment includes three key measures: advancing the initial dose of the vaccine from 3 months to 2 months of age, extending the interval between primary immunization doses from 1 month to 2 months, and adding an extra dose of acellular diphtheria-tetanus-pertussis vaccine at 6 years of age. This article discusses potential changes in the epidemiology and clinical manifestations of pertussis following such adjustments for immunization procedure, and awareness of these changes will facilitate the accurate identification of pertussis cases, which is crucial for evaluating the impact of these adjustments and further optimizing immunization strategies.
Humans ; Whooping Cough/epidemiology* ; Diphtheria-Tetanus-Pertussis Vaccine/immunology* ; Infant ; Immunization Schedule ; Child

BACKGROUND: The efficacy of routine childhood immunization depends on timely vaccine uptake and facility use patterns. This study examined the association between pediatric vaccination facility use patterns and routine childhood immunization uptake among children up to age eight years. METHODS: As part of the Kochi Adjunct Study of the Japan Environment and Children's Study (JECS), we analyzed data from 1,644 participants whose Maternal and Child Health Handbook photographs were collected in the eighth year of the cohort study. Maternal and Child Health Handbook records determined immunization completion. Participants were categorized into four groups based on pediatric vaccination facility use patterns: single facility use throughout, multiple facility use during the first period, multiple facility use during the second period, and multiple facility use throughout both periods. Maternal and child characteristics were collected via paper-based questionnaires. Associations between facility use patterns, sociodemographic factors, and immunization completion were analyzed using chi-square tests and logistic regression. RESULTS: Overall, routine childhood immunization completion was observed in 1,259 (76.6%) participants. Chi-square tests indicated that marital status, educational level, lower parity, never smoking, not attending nursery, and breastfeeding practice for infants aged four months old were significantly associated with routine childhood immunization completion. Single facility use throughout the immunization period was observed in 1,011 (61.5%) participants. Multiple facility use (38.5%) was associated with higher odds of routine childhood immunization incompletion than single facility use. This association was the strongest for those who used multiple facilities throughout the vaccination period (adjusted odds ratio, 1.90; 95% confidence interval, 1.24-2.91). CONCLUSIONS Single pediatric facility use was associated with higher routine immunization uptake. Our findings suggest that encouraging the use of one medical institution for a child's vaccinations may be a useful approach to consider when addressing vaccination coverage challenges.
Humans ; Japan ; Female ; Male ; Infant ; Child, Preschool ; Health Facilities/statistics & numerical data* ; Child ; Vaccination/statistics & numerical data* ; Adult ; Immunization/statistics & numerical data* ; Cohort Studies ; Infant, Newborn

BACKGROUND: Japan lacks comprehensive reports on the nationwide voluntary vaccine coverage. The effectiveness of public subsidies in promoting vaccination has not been fully investigated. Therefore, we aimed to estimate the nationwide coverage of voluntary vaccines, compare it with that of national immunization program (NIP)-included vaccines, and investigate the effectiveness of public subsidies. METHODS: We obtained nationwide monthly vaccine market data for rotavirus, Haemophilus influenzae type b (Hib), diphtheria, tetanus toxoid, acellular pertussis, inactivated poliovirus (DTaP-IPV), and mumps vaccines; estimated recipient numbers; and calculated coverage as the proportion of children from October 2011 to March 2022. Regarding the NIP-included vaccine, we compared vaccine coverage calculated from nationwide annual market data with that estimated by World Health Organization (WHO)/United Nations Children's Fund (UNICEF), using Bland-Altman analysis. RESULTS: The estimates of Hib and DTaP-IPV vaccine coverage derived from market data were slightly higher than the WHO/UNICEF estimates, with mean differences of 0.05 (95% CI: 0.02-0.07) for Hib and 0.03 (95% CI: 0.01-0.05) for DTaP-IPV. The coverage of the rotavirus vaccine gradually increased long before the implementation of national subsidies, reaching 0.9 in 2020. Hib vaccine coverage had already achieved 1.0 by January 2012. The coverage of the DTaP-IPV vaccine was approximately 0.6-0.8 in 2013, reaching 1.0 in 2014. The coverage of mumps vaccine increased gradually from 2011 to 2021. CONCLUSIONS Despite the possibility of overestimation, our estimates may serve as a valuable surrogate for actual vaccine coverage in Japan. An increasing trend in rotavirus and mumps vaccine coverage was observed when these vaccines were categorized as voluntary. Although vaccination policies differ from country to country, it would be beneficial to share findings on the impact of subsidies in Japan with other countries.
Japan ; Humans ; Vaccination Coverage/statistics & numerical data* ; Infant ; Immunization Programs/statistics & numerical data* ; Rotavirus Vaccines ; Haemophilus Vaccines ; Child, Preschool ; Poliovirus Vaccine, Inactivated ; Vaccines

OBJECTIVE: Vaccine hesitancy has been a public health issue for some time now, but gained more attention during COVID-19 pandemic. This systematic review aimed to estimate the prevalence of COVID-19 vaccination hesitancy and identify factors affecting it among adolescents. MATERIALS AND METHODS: The preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P 2020) was used. A search was performed in PubMed/ MEDLINE, EMBASE, Google Scholar, Herdin, and Cochrane databases on September 2023 using the key words: (COVID-19 OR SARS-COV OR corona virus) AND (Vaccination OR immunization) AND (adolescence OR teenagers OR youth) AND (hesitancy OR acceptance). Observational studies which determined the prevalence or risk factors for COVID-19 vaccine hesitancy among adolescents aged 10-19 years old were included. RESULTS: There were 5 good quality cross-sectional studies included. The prevalence of adolescents who did not want to be vaccinated ranged between 8.4% and 61.0%; while the prevalence of being unsure if they want to be vaccinated was between 31.6% and 88.0%. Factors associated with vaccine hesitancy included being economically disadvantaged, not having influenza vaccination, worrying about its effectiveness and safety, and low perceived necessity. CONCLUSION There is good quality evidence that COVID-19 vaccine hesitancy exists among adolescents. It is recommended that health workers should conduct information and education campaigns to iterate the effectiveness, safety, and misconceptions about of COVID-19 vaccination. Vaccination programs should also reach out to economically disadvantaged adolescents, and tapping parents and social media may be an effective strategy to improve vaccination acceptance among adolescents.
COVID-19 ; SARS-COV ; Severe acute respiratory syndrome-related coronavirus ; Vaccination ; Immunization ; Adolescent ; Adolescence ; Teenagers ; Youth

Objective To prepare mouse anti-human lymphocyte activation gene 3 (LAG3) monoclonal antibody (mAb) and perform immunological identification of the antibody. Methods BALB/c mice were immunized with LAG3-mLumin-3T3 cells, which stably express the extracellular and transmembrane regions of human LAG3 in mouse 3T3 cells. The secretion of anti-human LAG3 antibodies in mouse serum was assessed using flow cytometry and immunofluorescence. SP2/0 cells were injected subcutaneously into the mice to elicit solid myelomas, and mouse myeloma cells were subsequently isolated. Spleen cells from the immunized mice were fused with the myeloma cells to establish hybridomas, which were then separated using the limiting dilution method. Flow cytometry was used to detect LAG3 mAbs in the hybridoma culture medium. To map the epitopes recognized by these mAbs, 3T3 cells expressing individual extracellular domains of LAG3(LAG3 domains 1/-2/-3/-4-3T3) were used. Flow cytometry was also applied to analyze LAG3 expression on activated human peripheral blood mononuclear cells (PBMC) before and after co-culture with the LAG3 mAbs. Results Mice immunized with the recombinant eukaryotic cell antigen produced anti-LAG3 antibodies. The generated hybridomas secreted mouse anti-human LAG3 mAbs, with each hybridoma line recognizing different LAG3 antigenic domains. Conclusion Mouse anti-human LAG3 mAbs were successfully generated, with different hybridoma clones secreting antibodies that recognize distinct LAG3 epitopes. These findings lay the groundwork for further studies into the biological properties of LAG3 and the development of diagnostic reagents and therapeutic blocking antibodies for cancer treatment.
Animals ; Humans ; Mice ; Lymphocyte Activation Gene 3 Protein ; Antibodies, Monoclonal/immunology* ; Mice, Inbred BALB C ; Hybridomas/immunology* ; Antigens, CD/genetics* ; Immunization ; Recombinant Proteins/immunology* ; Female ; Eukaryotic Cells/immunology* ; Flow Cytometry ; Epitopes/immunology*

The aim of this study was to compare the immune responses of C57BL/6 mice immunized with two pathogens, foot-and-mouth disease virus (FMDV) and Senecavirus A (SVA), and to provide clues for revealing the regulatory mechanisms of acquired immunity. Inactivated and purified FMDV and SVA antigens were used to immunize C57BL/6 mice respectively, and the mice immunized with PBS were taken as the control. The percentages of Th1 and Th2 cells in the spleen lymphocytes of mice in each group were analyzed by flow cytometry at 14 and 28 days after immunization. RNA-Seq was performed for the spleen. Mouse macrophages were stimulated with the antigens in vitro to examine the expression of the differentially expressed genes (DEGs) screened out. The results showed that 14 days after immunization, there was no significant difference in the magnitude of the Th1/Th2 immune response elicited by the FMDV and SVA antigens. After 28 days, the magnitudes of the Th1 and Th2 immune responses elicited by the SVA antigen were higher than those elicited by the FMDV antigen. RNA-Seq revealed two common DEGs, Rsad2 and Tspan8, between the two immunization groups, which indicated that the two genes may be involved in the activation of the Th1/Th2 immune responses by FMDV and SVA antigens. FMDV and SVA antigens stimulated macrophages to secrete interleukin (IL)-12 and IL-33 in vitro, and the expression of Tspan8 and Rsad2 was consistent with the RNA-Seq results. The expression of Rsad2 was regulated by type I interferons (IFNα, IFNβ). In this study, we obtained the DEGs involved in the immune responses to the two antigens in mouse spleen, which provides a molecular basis for investigating the immune response mechanisms induced by FMDV and SVA.
Animals ; Foot-and-Mouth Disease Virus/genetics* ; Mice ; Spleen/cytology* ; Mice, Inbred C57BL ; Antigens, Viral/genetics* ; Transcriptome ; Th1 Cells/immunology* ; Immunization ; Viral Vaccines/immunology* ; Th2 Cells/immunology* ; Foot-and-Mouth Disease/immunology* ; Interleukin-33/genetics* ; Female ; Macrophages/immunology* ; Picornaviridae

To construct a recombinant Bacillus subtilis strain expressing SpaA and CbpB of Erysipelothrix rhusiopathiae for oral administration, we constructed the recombinant plasmid pDG1730-CBJA by fusion PCR and seamless cloning. The plasmid was introduced into B. subtilis KC strain by natural transformation, and the recombinant strain KC-spaA-cbpB was screened out on the plate containing spectinomycin (spe^r) and confirmed by PCR and starch degradation test. The SpaA and CbpB expressed by KC-spaA-cbpB were detected by Western blotting and indirect immunofluorescence assay, and the genetic stability of the recombinant strain in mice was determined. The plasmid pMAD-∆spe^r with knockout of spe^r was constructed and transformed into KC-spaA-cbpB. The spe^r-deleted mutant strain KC-spaA-cbpB: : ∆spe^r was screened and identified, and its immunogenicity in a mouse model was evaluated by oral immunization. The results showed that the recombinant strain KC-spaA-cbpB was stable in mice, expressing SpaA on the cell surface and CbpB on the spore surface. KC-spaA-cbpB: : ∆spe^r expressed SpaA and CbpB. The mice vaccinated with the spores of KC-spaA-cbpB: : ∆spe^r had higher levels of SpaA and CbpB-specific IgG in the serum that those vaccinated with the wild-type spores 42 days after vaccination by gavage (P < 0.01). The protective rate of mice immunized with the recombinant spores was 67.5%. The results indicated that a recombinant B. subtilis strain expressing SpaA and CbpB of E. rhusiopathiae was successfully constructed, and the recombinant strain laid a foundation for the development of oral live vector vaccines for swine erysipelas.
Animals ; Bacillus subtilis/immunology* ; Mice ; Erysipelothrix/immunology* ; Bacterial Proteins/immunology* ; Bacterial Vaccines/genetics* ; Erysipelothrix Infections/prevention & control* ; Immunization ; Mice, Inbred BALB C ; Plasmids/genetics* ; Immunogenicity, Vaccine ; Administration, Oral ; Antigens, Bacterial

To prepare a lipid nanoparticle (LNP)-based subunit vaccine of Mycobacterium tuberculosis (Mtb) antigen EsxV and study its immunological characteristics, the LNP containing EsxV and c-di-AMP (EsxV: C: L) was prepared by thin film dispersion method, and its encapsulation rate, LNP morphology, particle size, surface charge and polyphase dispersion index were measured. BALB/c mice were immunized with EsxV: C: L by nasal drops. The levels of serum and mucosal antibodies, transcription and secretion of cytokines in lung and spleen, and the proportion of T cell subsets were detected after immunization. EsxV: C: L LNPs were obtained with uniform size and they were spherical and negatively charged. Compared with EsxV: C immunization, EsxV: C: L mucosal inoculation induced increased sIgA level in respiratory tract mucosa. Levels of IL-2 secreted from spleen and ratios of memory T cells and tissue-resident T cells in mice were also elevated. In conclusion, EsxV: C: L could induce stronger mucosal immunity and memory T cell immune responses, which may provide better protection against Mtb infection.
Animals ; Mice ; Mycobacterium tuberculosis ; Antigens, Bacterial ; Immunization ; Nanoparticles ; Vaccines, Subunit ; Mice, Inbred BALB C