High Antibody Titers Research Articles

Evaluation of the safety and immune protection of OMPAC, PAPF, and EBPSs recombinant subunit vaccines Developed for Escherichia coli, Staphylococcus aureus, and Streptococcus agalactiae in mice.

Bacterial mastitis in dairy cow is often caused by a combination of bacterial infections, such as Escherichia coli, Staphylococcus aureus, and Streptococcus agalactiae. Currently, there is no effective vaccine against the disease. Therefore, we constructed a recombinant subunit vaccine by fusing gene fragments of E. coli OMPA and OMPC, S. aureus EBPS, and S. agalactiae PGK, AP1, AP2, and FBSA. These gene fragments were combined into three fusion proteins: OMPAC, EBPSs, and PAPF. Mice were immunized with the three fusion proteins either alone or in combination. The test results showed that immunization with OMPAC, EBPSs, and PAPF individually or in combination could induce high titers of antibodies in the mice. Additionally, 21days post-immunization, IFN-γ levels were significantly increased in all groups of mice, suggesting that immunization with OMPAC, EBPSs, and PAPF, whether alone or in combination, was effective in inducing antibody production. This indicates that OMPAC, EBPSs, and PAPF were effective in inducing both humoral and cellular immunity in mice. Furthermore, immunization with OMPAC, EBPSs, and PAPF individually or in combination were effective in protecting mice from E. coli, S. aureus, and S. agalactiae infections. Importantly, a mixture of the three fusion proteins was relatively safe for pregnant female mice. In conclusion, we successfully constructed and expressed recombinant subunit vaccines of OMPAC, EBPSs and PAPF and verified that these vaccines rapidly induced high levels of specific antibodies while reducing bacterial loads in the organs of mice. This lays the theoretical foundation and data support for the development of novel subunit vaccines against mastitis in dairy cows.

Biogenic silver nanoparticle as an adjuvant in an S1 subunit recombinant vaccine.

Adjuvants are crucial for maintaining specific, protective, and long-lasting immunity. Here, we aimed to evaluate the antigenic and immunogenic activity of a recombinant form of the S1 domain of the Spike protein, associated with biogenic silver nanoparticles (bio-AgNP) and Alhydrogel® as an alternative and conventional adjuvant, respectively, for a SARS-CoV-2 subunit vaccine. We produced and evaluated the antigenicity of the recombinant S1 (rS1) protein by testing its recognition by antibodies present in SARS-CoV-2 positive human serum. The immunogenicity of the rS1 protein was assessed in vivo by its ability to induce antibody production in mice. Furthermore, we sought to establish the types of humoral and cellular immune responses generated through intramuscular immunization in BALB/c mice with the rS1 + bio-AgNP vaccine. The recombinant S1 (rS1) protein was successfully cloned, expressed in Escherichia coli, and confirmed to have strong antigenic potential, being recognized by human antibodies up to a 1:51,200 serum dilution. In vivo assays showed that vaccines using rS1 with either bio-AgNP or Alhydrogel® as adjuvants induced high and consistent antibody titers (1:51,200) and a range of antibody isotypes in mice. Cellular immune response analysis revealed significant IL-10 expression with rS1 + bio-AgNP and both IL-10 and TNFα expression with rS1 + Alhydrogel®. These results support rS1 + bio-AgNP as a promising vaccine candidate for future development, highlighting its potential not only as a viable alternative to traditional adjuvants but also as an innovative contribution to advancing more effective and accessible immunological strategies.

Virus-like particle-based vaccines targeting the Anopheles mosquito salivary protein TRIO.

Malaria is a highly lethal infectious disease caused by Plasmodium parasites. These parasites are transmitted to vertebrate hosts when mosquitoes of the Anopheles genus probe for a blood meal. Sporozoites, the infectious stage of Plasmodium, transit to the liver within hours of injection into the dermis. Vaccine efforts are hindered by the complexity of the parasite's lifecycle and the speed at which the infection is established in the liver. In an effort to enhance immunity against Plasmodium, we produced a virus-like particle (VLP)-based vaccine displaying an epitope of TRIO, an Anopheles salivary protein that has been shown to enhance mobility and dispersal of sporozoites in the dermis. Previous work demonstrated that passive immunization with TRIO offered protection from liver infection and acted synergistically with a Plasmodium-targeted vaccine. Immunization of mice with TRIO VLPs resulted in high-titer and long-lasting antibody responses that did not significantly drop for over 18 months post-immunization. TRIO VLPs were similarly immunogenic when combined with an anti-malaria vaccine targeting the L9 epitope of the Plasmodium falciparum circumsporozoite protein. However, when used in a malaria challenge mouse model, TRIO VLPs only provided modest protection from infection and did not boost the protection provided by L9 VLPs.IMPORTANCEProteins present in the salivary glands of mosquitos have been shown to enhance the transmission efficiency of mosquito-borne pathogens, suggesting that interventions targeting the activity of these proteins could reduce transmission. Here, we looked at the efficacy of a vaccine targeting TRIO, an Anopheles mosquito salivary protein that has been reported to enhance Plasmodium falciparum malaria infection. We show that this vaccine can elicit strong anti-TRIO antibody responses, but these antibodies only result in a modest decrease in infection.

Capvaxive (V116): A new frontier in the prevention of pneumococcal pneumonia and invasive disease

Pneumococcal Pneumonia (PP) and Invasive Pneumococcal Disease (IPD), both highly contribute to the rate of morbidity and mortality in adults around the globe. They are caused by the bacteria called Streptococcus pneumoniae. According to a population-based study, the Global Incidence Rate of PP cases was 90.7 per 100,000 person-years, with a 7.6% case-fatality rate [1]. For adults Pneumococcal Conjugate Vaccines (PCVs), mainly PCV15 and PCV 20, along with Pneumococcal polysaccharide vaccine (PPSV23) are currently recommended by the Centers for Disease Control and Prevention. Among these already vaccines, arises Capvaxive (V116) by Merck for active immunization for the prevention of PP and IPD. Capvaxive, also known as pneumococcal 21-conjugate vaccine recently approved by the FDA for active immunization for prevention of pneumonia and invasive disease caused by 21 different serotypes of streptococcus pneumoniae in adults [2]. It is administered as a single intra-muscular dose of 0.5 ml. It stimulates the body's immune response by antigenic stimulation, leading to opsonophagocytic activity [OPA] against invasive S. Pneumoniae. It is known to induce OPA by activation of macrophages and neutrophils for engulfment and phagocytosis of bacterial cells [3]. Multiple trials have been conducted all over the world as reported to understand the safety, tolerability, and immunogenicity. Studies conducted resulted in non-inferiority to its comparator PPSV23 [4,5], encouraging its development for safety against S. Pneumoniae. Neither of the studies reported vaccine-related serious adverse effects or deaths. The most common adverse effect reported was solicited infusion site reaction, reported in up to 73% of participants [4]. When compared, Capvaxive infused participants had a higher antibody titer and induced immune response against all 21 serotypes, with a similar safety profile to its comparators. It notably had a more immunogenic reaction against the 9 unique serotypes, previously not targeted in PPSV23 [4]. As the newly FDA approved vaccine enters the market, it is crucial to keep track of its safety and tolerability as it reaches a wider population. It is a notable landmark of pharmacology to target 21 variants of S. Pneumonia which has been proved to be lethal in the past as it causes mortal pneumonia. As reported to have low levels of systemic side effects on patients infused with this vaccine, this is a step forward in encountering the deadly S. Pneumonia with more than 100 serotypes known to man.

Comparison of Long-Term Antibody Titers in Calves Treated with Different Conjunctival and Subcutaneous Brucella abortus S19 Vaccines.

Brucellosis is still the most common zoonosis worldwide despite advanced technology and animal husbandry. Since there is still no effective Brucella vaccine for humans, it is crucial to control the disease in ruminants through eradication and vaccination. Although some countries around the world have achieved this circumstance, every country aims to become free of Brucellosis through vaccination, animal movements, and various eradication measures. For this purpose, the Brucella abortus S19 strain has been used safely for about 100 years. However, due to the O-polysaccharide (OPS) antigen in its structure, the antibody response created by the vaccine causes confusion in serological tests. For this purpose, researchers have provided both mucosal immunity and short-term antibody response by using the B. abortus S19 vaccine in conjunctival form instead of subcutaneous form. This study aimed to determine how long the post-vaccination titer levels persisted in animals vaccinated with vaccines from 3 different companies and different routes. In this study, a total of 115 calves aged 3 to 4.5 months were created in five groups, with 23 animals in each group: group 1 (vaccine brand A), group 2 (vaccine brand B), and group 3 (vaccine brand C) received the two-dose conjunctival vaccine, group 4 received the single-dose subcutaneous vaccine (vaccine brand C), and group 5 received the subcutaneous vaccine (vaccine brand C) plus the booster dose conjunctival vaccine (vaccine brand B). Brucellosis antibody titers were monitored each 21 days until the cattle were 26-28 months old. The collected sera were analyzed using the Rose Bengal Plate Test (RBPT), Serum Agglutination Test (SAT), and Complement Fixation Test (CFT), which are the preferred serological methods for Brucellosis eradication plans worldwide. In the conjunctival vaccination groups, only 3 (13%) of the animals in group 1 developed antibody titers one month after vaccination, and there was no antibody response detected against Brucellosis in group 2 and group 3. In animals that were stimulated conjunctivally, the threshold value of 30 International CFT Units (ICFTUs) (for distinguishing between infective titers and vaccination titers) was observed in one animal each in group 1 and group 2 and 0 animal in group 3. It was found that antibody titers turn to Brucellosis negative in all conjunctival vaccine groups at 7 months after vaccination. In groups 4 and 5, the first-month serological screening detected over 30 ICFTUs in 17 (89.47%) animals and 16 (69.5%) animals, respectively. In group 4, CFT titers were found to fall below 30 on the 17th month and 9.3 on the 22nd month. On the 14th month, the CFT titers of group 5 were found to be below 30, and all animals in this group turned negative after the 19th month. It was found that the single dose B. abortus S19 subcutaneous vaccination in calves caused persistent antibodies in 5% of the population. It is believed that persistent and high antibody titers created by subcutaneous vaccines will cause false positivity and create confusion in Brucellosis eradication programs. Therefore, although there is no clear distinction between vaccinated and infected animals, it has been observed that conjunctival Brucellosis vaccines create more stable antibody titers and decrease rapidly compared to subcutaneous vaccines. Based on the results of this study and the advantages of conjunctival vaccines, more effective eradication programs and antibody monitoring can be carried out in vaccinated herds where Brucellosis outbreaks are observed.

T4 Phage Displaying Dual Antigen Clusters Against H3N2 Influenza Virus Infection.

The current H3N2 influenza subunit vaccine exhibits weak immunogenicity, which limits its effectiveness in preventing and controlling influenza virus infections. In this study, we aimed to develop a T4 phage-based nanovaccine designed to enhance the immunogenicity of two antigens by displaying the HA1 and M2e antigens of the H3N2 influenza virus on each phage nanoparticle. Specifically, we fused the Soc protein with the HA1 antigen and the Hoc protein with the M2e antigen, assembling them onto a T4 phage that lacks Soc and Hoc proteins (Soc-Hoc-T4), thereby constructing a nanovaccine that concurrently presents both HA1 and M2e antigens. The analysis of the optical density of the target protein bands indicated that each particle could display approximately 179 HA1 and 68 M2e antigen molecules. Additionally, animal experiments demonstrated that this nanoparticle vaccine displaying dual antigen clusters induced a stronger specific immune response, higher antibody titers, a more balanced Th1/Th2 immune response, and enhanced CD4+ and CD8+ T cell effects compared to immunization with HA1 and M2e antigen molecules alone. Importantly, mice immunized with the T4 phage displaying dual antigen clusters achieved full protection (100% protection) against the H3N2 influenza virus, highlighting its robust protective efficacy. In summary, our findings indicate that particles based on a T4 phage displaying antigen clusters exhibit ideal immunogenicity and protective effects, providing a promising strategy for the development of subunit vaccines against various viruses beyond influenza.

Potential role of TRAF2 in pulmonary hypertension in broiler chickens and preparation and specificity analysis of its polyclonal antibody.

Due to the lack of specific antibody anti-chicken tumor necrosis factor receptor-associated factor 2 (TRAF2), it is difficult to further explore the role of TRAF2 in pulmonary artery remodeling in pulmonary hypertension(PH) in broilers. In this experiment, we prepared a polyclonal antibody to TRAF2 by constructing a TRAF2 recombinant protein prokaryotic expression vector and analyzed the expression of TRAF2 in in vivo and in vitro models of pulmonary hypertension in broiler chickens and the effect of TRAF2 on the activity and apoptosis of PASMCs. The results showed that after immunization with TRAF2 recombinant protein we obtained high titers of polyclonal antibodies, and astragalus polysaccharide as an immune adjuvant could enhance the effect of immunization. Antibody specificity showed that the TRAF2 polyclonal antibody specifically bound to TRAF2 protein in chickens and ducks but weakly to TRAF2 protein in rabbits, mice and goats.TRAF2 was significantly upregulated in an in vivo and in vitro model of PH in broilers. Knockdown of TRAF2 inhibited the activity of PASMCs and induced apoptosis in PASMCs. Our study lays the foundation for further research on the pathomechanism of PH in broiler chickens and provides new targets for its prevention and drug development.

Dissociation of IgM antibodies from red blood cells using ethylenediamine tetraacetate/glycine acid or chloroquine diphosphate.

Ethylenediamine tetraacetate/glycine acid (EGA) and chloroquine diphosphate (CDP) are used in transfusion testing to dissociate IgG antibodies from red blood cells (RBCs). However, the ability of these reagents to dissociate IgM antibodies sensitized to RBCs has not been comprehensively elucidated. We investigated whether EGA and CDP could dissociate cold-reactive antibodies from RBCs and their effect on RBCs after dissociation treatment. Cold-reactive antibody-sensitized RBC samples were prepared by mixing group A RBCs and group B plasma and treated with EGA, CDP, and dithiothreitol (DTT). Before and after the dissociation treatment, changes in the agglutination of these RBCs were assessed using the test tube method. Flow cytometric analysis was used to confirm the nature of antibodies bound to RBCs. Additionally, RBC morphology was evaluated using scanning electron microscopy. This study utilized off-label use of EGA and CDP. Flow cytometric analysis showed that antibodies sensitized to RBCs were mainly IgM antibodies. After antibody dissociation, agglutination disappeared in the EGA-treated samples to the same degree as in the DTT-treated samples. However, IgM antibodies remained in the CDP-treated samples. Regarding RBC morphology, RBC surface appeared coarser in both EGA- and CDP-treated samples, and RBC area was significantly smaller in the CDP-treated samples than in the EGA-treated samples. EGA could dissociate cold-reactive antibodies, whereas CDP had a higher residual antibody content. This difference in dissociation ability appears to correlate with the antibody pH of the dissociation reagent. EGA treatment may be useful in cases of sensitization by high-titer cold-reactive antibodies.

Analysis of antibody detection data of Mycoplasma pneumoniae in a hospital in Beijing City from 2017 to 2024

Objective: To explore the distribution characteristics of Mycoplasma pneumoniae (MP) antibody detection data in hospital, provide data reference for the prevention and control of MP infections. Methods: A single-center retrospective study was conducted on 20 639 patients with suspected Mycoplasma pneumoniae (MP) infection from March 2017 to February 2024 at the outpatient, emergency, and inpatient departments of Peking University Third Hospital. The age range was from 0 to 105 years, with 11 286 males and 9 353 females. The passive agglutination method was used to detect MP antibodies in patient serum, and SPSS 22.0 statistical software was used for statistical analysis. The χ2 test was used to analyze the differences in positive rates of MP antibodies among different genders, age groups, seasons, years, and antibody titers. The trend χ2 test was used to analyze the trend of detection rates with age changes. Results: Among the 20 639 patients, the positive rate of MP antibodies was 23.19%(4 786/20 639), with a higher positive rate in females was 27.16%(2 540/9 353) compared to males (19.90%, 2 246/11 286;χ²=151.191, P<0.01). The positive rate in children was 37.13%(2 731/7 356)significantly higher than in adults(15.47%, 2 055/13 283;χ²=1 246.433, P<0.01). The 6 to <12 year age group (63.11%, 1 223/1 938) had the highest positive rate of MP antibodies, followed by 12 to <18 year old group (56.78%, 385/678). The positive rate of MP antibodies increased with age from 0 to 12 years old but gradually decreased after 12 to <18 years old (χ2=3 848.393, P trend<0.01). The annual MP antibody positivity rates from 2017 to 2023 were 26.92%, 29.23%, 27.46%, 18.43%, 17.16%, 11.89%, and 23.72%, respectively, with statistically significant differences among the years (χ²=387.519, P<0.01). The MP antibody positive rate was high in autumn over the course of 7 years (χ²=242.560, P<0.01). The positive rates of MP antibodies for the years 2017-2019, 2020-2022, and 2023-2024 are (28.00%, 16.60%, 21.84%), respectively, with statistically significant differences among the three periods(χ²=295.845, P<0.01).The monthly positive rates of MP antibody in different years were (5.63% to 43.11%). In the MP antibody titer, qualitative testing was conducted on 4 563 patients and 16 076 patients had a semi-quantitative MP antibody titer of ≥1∶160 with a positive rate of 16.03%(2 577/16 076). Among the proportion of children with high titers of MP antibodies ≥1∶1 280 was 11.11%(798/7 182). Conclusion: The positive rates of MP antibodies in hospital in the Beijing area vary among different genders, ages, and seasons, with a higher incidence in autumn, mainly among children and adolescents.

Seroprevalence of Toxoplasma gondii in White-Tailed Deer (Odocoileus virginianus) in New York State.

The parasitic protozoa, Toxoplasma gondii (T. gondii), is a model organism for one health because of its wide-ranging impacts on humans, wildlife, and domestic animals. Intermediate hosts, including white-tailed deer (Odocoileus virginianus), have been implicated in its maintenance. Prior analysis of Toxoplasma gondii seroprevalence in New York State deer focused on rural areas; however, the high density of domestic cats (Felis catus) in urban areas has been implicated in its spread amongst deer. To address this, the seroprevalence of Toxoplasma gondii was assessed across two suburban and urban areas with known deer overabundance in Onondaga and Suffolk County. Here, domestic cats are the only likely definitive host. Between 2019 and 2023, serum from culled deer was collected, and Toxoplasma gondii seropositivity was determined using the modified agglutination test. Overall seroprevalence was 49.31% (n = 144) but was significantly higher in Onondaga (64%) compared to Suffolk County (36%), despite similarities between these two regions. Deer from Onondaga also had higher antibody titers. These data suggest that although urbanization may be a predictor of Toxoplasma gondii seropositivity in deer, there are additional contributing factors. Overall, this study emphasizes the need for continued surveillance in intermediate hosts and informs public health and wildlife management decisions aimed at limiting the impact of Toxoplasma gondii.

A self-assembled nanoparticle vaccine elicits effective neutralizing antibody response against EBV infection.

Epstein-Barr virus (EBV) is a significant global public health concern because of its association with various malignancies and autoimmune diseases. Over 90% of the global population is chronically infected with EBV, impacting numerous cancer-related cases annually. However, none of the effective prophylactic vaccines against EBV is approved at present. In this study, we developed a novel vaccine candidate based on epitope peptides from the receptor-binding domain of EBV-encoded gp350 glycoprotein to prevent EBV infection. These epitope peptides detected a binding capability with host cells were then fused by flexibility linkers and expressed in Escherichia coli to reduce the unnecessary glycan modifications to simulate their free-glycan status. The fused recombinant protein (L350) was displayed on the surface of ferritin-based nanoparticle. The immunogenicity of the L350-ferritin nanoparticle was evaluated in Balb/c mice, and the neutralizing titers of sera from immunized mice were detected by means of an infection blocking assay in an in vitro cell model. All the five epitope peptides could bind to AKATA cells, and their fused recombinant protein (L350) was successfully presented on the surface of self-assembled ferritin nanoparticles. Sera from the L350-ferritin nanoparticle-immunized mice showed high titers of both L350 protein-specific and gp350D123 protein-specific antibodies, and sera from gp350D123 protein-immunized mice could also recognize L350 protein well. Most importantly, the L350-ferritin nanoparticle induced efficient neutralizing antibodies to block EBV-GFP infection in AKATA cells and also constructed a strong antigen-specific B-cell memory in immunized mice. Moreover, histopathological changes of main tissues from all vaccinated mice were not observed. These data indicate that the L350-ferritin nanoparticle vaccine candidate has considerable potential application in preventing EBV infection and provides a promising basis for developing prophylactic EBV vaccines.

Exploring the Relationship Between Humoral and Cellular T Cell Responses Against SARS-CoV-2 in Exposed Individuals From Emilia Romagna Region and COVID-19 Severity.

COVID-19 remains a significant global health problem with uncertain long-term consequences for convalescents. We investigated the relationships between anti-N protein antibody levels, severe acute respiratory syndrome (SARS)-CoV-2-associated TCR repertoire parameters, HLA type and epidemiological information from three cohorts of 524 SARS-CoV-2-infected subjects subgrouped in acute phase, seronegative and seropositive convalescents from the Emilia Romagna region. Epidemiological information and anti-N antibody index were associated with TCR repertoire data. HLA type was inferred from TCR repertoire using the HLA3 tool and its association with clonal breadth (CB) and clonal depth (CD) was assessed. Age above 58 years, male and COVID-19 hospitalisation were significantly and independently associated with seropositivity (p = 0.004; p = 0.004; p = 0.04), suggesting an association between high antibody titres and symptoms' severity. As for the TCR repertoire analysis, we found no difference in CB among the cohorts, while CD was higher in seronegative than acute (p = 0.04). However, clustering analysis supported that seronegative patients are endowed with broader CB and deeper CD indicating a compensatory mechanism without effective seroconversion. The CD calculated on the TCRs associated with the single SARS-CoV-2 ORFs in convalescents is higher when compared to the acute. Lastly, we identified and reported on novel HLAs significantly associated with increased risk of hospitalisation such as HLA-C*07:02 carriers (OR = 3.9, CI = 1.1-13.4, p = 0.03) and on HLAs that associate significantly with lower or higher TCR repertoire parameters in a population exposed for the first time to SARS-CoV-2.

Efficacy of lipid nanoparticles-based vaccine to protect against vulvovaginal candidiasis (VVC): Implications for women's reproductive health.

Vulvovaginal candidiasis (VVC) is a common women's health issue, with rising antifungal resistance. This study was aimed to prepare and evaluate the efficacy of a lipid nanoparticle-based vaccine in a murine model of VVC. Dried and reconstituted vesicles containing C. albicans antigens (DRNPs-Ca-Ags) vaccine, formulated with phosphatidylcholine and cholesterol-based lipid nanoparticles via film hydration and freeze-drying. The safety evaluation of DRNPs-CaAgs was conducted by determining hepatic (AST, ALT) or renal (BUN, creatinine) biomarkers. Female mice were immunized with DRNPs-CaAgs or Alum-CaAgs, and immune responses were evaluated via antibody titers, IgG isotypes, and splenocyte proliferation. Protective efficacy of vaccine formulations was assessed through fungal burden, biofilm formation, cytokine levels, and histopathological analysis of vaginal tissues. Mice vaccinated with DRNPs-CaAgs showed significantly enhanced immune responses, with higher antibody titers and IgG2a levels as compared to the Alum-CaAgs group. Vaginal fungal burden was dramatically reduced (665±78 CFUs in DRNPs-CaAgs immunized group vs. 12,944±3540 CFUs in Alum-CaAgs group, p<0.01). Biofilm formation decreased by 45% (p<0.05), and inflammatory cytokines were significantly lowered. Histopathological analysis revealed minimal tissue damage in DRNPs-CaAgs vaccinated mice. The findings suggest DRNPs-CaAgs as a promising vaccine for VVC, eliciting strong immunity, reducing fungal load, and minimizing inflammation. While the reliance on a murine model is a limitation, future clinical trials are essential to evaluate its efficacy and safety in humans, offering a potential strategy to combat drug-resistant infections and improve women's reproductive health.

Malaria: Factors affecting disease severity, immune evasion mechanisms, and reversal of immune inhibition to enhance vaccine efficacy.

Malaria is a complex parasitic disease caused by species of Plasmodium parasites. Infection with the parasites can lead to a spectrum of symptoms and disease severity, influenced by various parasite, host, and environmental factors. There have been some successes in developing vaccines against the disease recently, but the vaccine efficacies require improvement. Some issues associated with the difficulties in developing a sterile vaccine include high antigenic diversity, switching expression of the immune targets, and inhibition of immune pathways. Current vaccine research focuses on identifying conserved and protective epitopes, developing multivalent vaccines (including the whole parasite), and using more powerful adjuvants. However, overcoming the systematic immune inhibition and immune cell dysfunction/exhaustion may be required before high titers of protective antibodies can be achieved. Increased expression of surface molecules such as CD86 and MHC II on antigen-presenting cells and blocking immune checkpoint pathways (interactions of PD-1 and PD-L1; CTLA-4 and CD80) using small molecules could be a promising approach for enhancing vaccine efficacy. This assay reviews the factors affecting the disease severity, the genetics of host-parasite interaction, immune evasion mechanisms, and approaches potentially to improve host immune response for vaccine development.

Immunogenicity, Efficacy, and Effectiveness of Two-Dose and Shorter Schedules of Hepatitis E Vaccine: A Systematic Review.

Background: Hepatitis E virus (HEV) is a leading cause of acute viral hepatitis in adults. The schedule for HEV 239, the only approved anti-HEV vaccine, consists of three doses at 0, 1, and 6 months, which is unsuitable for use in emergency and outbreak situations where quick protection is desired. We, therefore, undertook a systematic review of data on immunogenicity, efficacy, and effectiveness of alternative accelerated schedules. Methods: Data sources on immunogenicity, efficacy, and effectiveness of the HEV 239 vaccine following accelerated schedules published between 22 January 2005 and February 2024 were identified from five electronic databases, and the relevant data were extracted. Results: The search identified seven relevant reports, including one phase II pre-licensure trial, three reports from the phase III licensure trial, and three post-licensure reports. In these studies, following administration of the HEV 239 vaccine in two doses at 0 and 1 month or a three-dose rapid (0, 7, and 21 days) schedule, anti-HEV antibody seroconversion rates were similar to and geometric mean concentrations of anti-HEV antibody were only slightly lower than those following the standard three-dose schedule. In individuals who were seropositive for anti-HEV antibodies at baseline, the antibody response persisted for several years irrespective of the number of vaccine doses, and in those who were seronegative at baseline, administration of two vaccine doses induced antibodies whose level remained substantially high till at least 13 months of follow-up. Administration of two doses was also associated with a high protective efficacy against HEV infection and associated disease. Conclusions: The available data indicate that two doses of HEV 239 administered one month apart confer sufficiently high antibody titers and protection for at least 13 months, a duration which should be adequate for its use as an outbreak control measure.

Bilateral femoral neck fractures and fixation failure due to stiff-person syndrome.

We describe a woman with stiff-person syndrome (SPS), whose muscle spasms resulted in sequential bilateral femoral neck fractures. Orthopaedic fixation of the first fracture was complicated by increased muscle spasm, fracture nonunion and ultimately metalwork fracture. SPS was diagnosed following the fracture of the contralateral femoral neck, neurology assessment and detection of high-titre antibodies to glutamic acid decarboxylase. Multidisciplinary management with high-dose benzodiazepines, intravenous immunoglobulin infusions, and bilateral total hip replacements achieved a good functional outcome. Spasms associated with SPS are a rare cause of pathological fractures and may cause orthopaedic fixation to fail. Early recognition and multidisciplinary care are essential to prevent additional morbidity.

Intranasal influenza-vectored vaccine expressing pneumococcal surface protein A protects against Influenza and Streptococcus pneumoniae infections

Streptococcus pneumoniae and influenza A virus (IAV) are significant agents of pneumonia cases and severe respiratory infections globally. Secondary bacterial infections, particularly by Streptococcus pneumoniae, are common in IAV-infected individuals, leading to critical outcomes. Despite reducing mortality, pneumococcal vaccines have high production costs and are serotype specific. The emergence of new circulating serotypes has led to the search for new prevention strategies that provide a broad spectrum of protection. In this context, vaccination using antigens present in all serotypes, such as Pneumococcal Surface Protein A (PspA), can offer broad coverage regardless of serotype. Employing the reverse genetics technique, our research group developed a recombinant influenza A H1N1 virus that expresses PspA (Flu-PspA), through the replacement of neuraminidase by PspA. This virus was evaluated as a bivalent vaccine against infections caused by influenza A and S. pneumoniae in mice. Initially, we evaluated the Flu-PspA virus’s ability to infect cells and express PspA in vitro, its capacity to multiply in embryonated chicken eggs, and its safety when inoculated in mice. Subsequently, the protective effect against influenza A and Streptococcus pneumoniae lethal challenge infections in mice was assessed using different immunization protocols. Analysis of the production of antibodies against PspA4 protein and influenza, and the binding capacity of anti-PspA4 antibodies/complement deposition to different strains of S. pneumoniae were also evaluated. Our results demonstrate that the Flu-PspA virus vaccine efficiently induces PspA protein expression in vitro, and that it was able to multiply in embryonated chicken eggs even without exogenous neuraminidase. The Flu-PspA-based bivalent vaccine was demonstrated to be safe, stimulated high titers of anti-PspA and anti-influenza antibodies, and protected mice against homosubtypic and heterosubtypic influenza A and S. pneumoniae challenge. Moreover, an efficient binding of antibodies and complement deposition on the surface of pneumococcal strains ascribes the broad-spectrum vaccine response in vivo. In summary, this innovative approach holds promise for developing a dual-protective vaccine against two major respiratory pathogens.

Clinical observation and anti-drug antibody monitoring of enzyme replacement therapy in children with Fabry disease

Objective: To analyze the efficacy of enzyme replacement therapy and anti-drug antibody production in children with Fabry disease. Methods: The clinical data of 7 children with Fabry disease treated with enzyme replacement therapy for more than 1 year at Children's Hospital of Zhejiang University School of Medicine from July 2021 to June 2024 were retrospectively analyzed. The basic information and the changes of related clinical indicators before and after treatment were collected. Paired sample t test was used to compare renal function, left heart mass index, pain score and other related indexes before and after treatment. The anti-drug antibodies were detected by enzyme-linked immunosorbent assay. Results: A total of 6 boys and 1 girl were included. The age of diagnosis was (12.2±1.8) years. After 1 year of enzyme replacement therapy, the abnormal substrate globotriaosylsphingosine and brief pain inventory scores of all children were significantly lower than those before treatment ((16±11) vs. (63±42) μg/L, 22±19 vs. 45±29, t=3.88, 3.43, both P<0.05). There were no significant differences in glomerular filtration rate, urinary microalbumin to creatinine and left heart mass index before and after treatment ((124±35) vs. (136±26) ml/(min·1.73 m2), (9.3±8.3) vs. (3.8±2.5) mg/g, (38±9) vs. (33±6) g/m2.7, t=1.33, 1.74, 1.19, all P>0.05). Patients 4, 5 and 6 developed anti-drug antibodies at 1 month, 4 months and 1 month after medication, respectively. Patient 4 had persistently high anti-drug antibody titers (absorbance 3.65-3.73) accompanied by urticaria, elevated globotriaosylsphingosine and worsening clinical symptoms. Conclusions: The enzyme replacement therapy can effectively improve the clinical symptoms and reduce the level of globotriaosylsphingosine in children with Fabry disease. The anti-drug antibody is common in patients after long-term enzyme replacement therapy and may diminish the efficacy, which needs dynamic monitoring.

Double-negative T cells in pediatric rheumatic diseases.

Double-negative (CD4-CD8-) T (DNT) cells have been implicated in autoimmune lymphoproliferative syndrome (ALPS), where their expansion inside the circulating pool of T cells represents a diagnostic criterion. Recent experimental evidence has supported the immunomodulatory roles of DNT cells, and studies in adult patients have suggested that they may be altered in some immune-mediated conditions. This study aimed to retrieve available data on circulating DNT cells in pediatric rheumatic disorders that do not arise in the context of ALPS through a systematic literature review of 3 scientific databases (PubMed, Scopus, and Web of Science). The final output of the systematic literature search consisted of 8 manuscripts, including cross-sectional (n=6) and longitudinal (n=2) studies. Overall, the pooled population of patients includes children affected with pediatric systemic lupus erythematosus (n= 104), juvenile idiopathic arthritis (n=92), Behçet's disease (n=15), mixed connective tissue disease (n=8), juvenile dermatomyositis (n=6), and Kawasaki disease/multisystem inflammatory disease in children (n=1 and n=14, respectively); moreover, one study also included 11 children with a high titer of antinuclear antibody but no diagnosis of rheumatic disease. All studies except one included a control group. The number of DNT cells were increased in most studies of children with rheumatic diseases. Even if such a limited number of studies and their great heterogeneity in several methodological aspects do not allow for reliable conclusions about the relevance of DNT cells in specific rheumatic conditions in children, this cell population deserves further investigation in this pathological setting through well-designed clinical studies.

Mycobacterium tuberculosis infection complicated by talaromycosis in a patient with positive anti-interferon-γ autoantibodies: a case report

High-titer antibodies to interferon-gamma (IFN-γ) are strongly correlated with infections caused by intracellular pathogens, particularly non-tuberculous mycobacteria and Talaromyces marneffei (TM). However, cases of concurrent infections with TM and Mycobacterium tuberculosis (MTB) in non-immunosuppressed patients are extremely rare. We presented a clinical case of a patient with anti-IFN-γ autoantibodies who developed an MTB infection complicated by Talaromyces marneffei, which subsequently led to secondary hemophagocytic syndrome. This report aimed to raise clinicians' awareness of this rare association to minimize the risk of misdiagnosis and overdiagnosis.