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In vaccine design, antigens are often arrayed in a multivalent nanoparticle form, but in vivo mechanisms underlying the enhanced immunity elicited by such vaccines remain poorly understood. We compared the fates of two different heavily glycosylated HIV antigens, a gp120-derived mini-protein and a large, stabilized envelope trimer, in protein nanoparticle or “free” forms after primary immunization. Unlike monomeric antigens, nanoparticles were rapidly shuttled to the follicular dendritic cell (FDC) network and then concentrated in germinal centers in a complement-, mannose-binding lectin (MBL)–, and immunogen glycan–dependent manner. Loss of FDC localization in MBL-deficient mice or via immunogen deglycosylation significantly affected antibody responses. These findings identify an innate immune–mediated recognition pathway promoting antibody responses to particulate antigens, with broad implications for humoral immunity and vaccine design.

Background Brucellosis is listed as a priority disease in low-income countries like Guinea, facing challenges in logistics, equipment, competence, and cost limitations for diagnosis. Serological diagnosis is mainly performed by the Rose Bengal agglutination test (RBT) in the veterinary sector. We have compared its discriminative capacity with more sophisticated and expensive serological tests, such as multi-species or species-specific ELISA kits and Complement Fixation test (CFT). Methodology/principal findings A panel of 554 serum samples of pigs, goats, sheep, and cattle collected throughout Guinea from 2017 to 2019 where tested by RTB and ELISA tests in parallel at the Institut Pasteur de Guinée (Conakry) and the Brucellosis WOAH/EU Reference Laboratory of the French Agency for Food, Environmental and Occupational Health & Safety (Maisons-Alfort, France). ELISAs performed equally across laboratories (Kappa =0.867–0.958); RBT and ELISA showed 94–95% concordance. The CFT value of positive cattle samples also logically followed the RBT scores Conclusions/significance In low-income countries like Guinea, the less expensive RBT can be regarded as a convenient routine Brucella diagnosis tool, assuming a solid experience of the operator following standard operating protocols and regular proficiency tests. As WOAH recommends confirmatory methods, the multispecies ELISA kit appears as a good candidate for conveniently trained and equipped laboratories.

The Plasmodium falciparum circumsporozoite protein (CSP) forms the basis of leading subunit malaria vaccine candidates. However, the mechanisms and specific targets of immunity are poorly defined. Recent findings suggest that antibody-mediated complement-fixation and activation play an important role in immunity. Here, we investigated the regions of CSP targeted by functional complement-fixing antibodies and the antibody properties associated with this activity. We quantified IgG, IgM, and functional complement-fixing antibody responses to different regions of CSP among Kenyan adults naturally exposed to malaria (n=102) and using a series of rabbit vaccination studies. Individuals who acquired functional complement-fixing antibodies had higher IgG, IgM and IgG1 and IgG3 to CSP. Acquired complement-fixing antibodies targeted the N-terminal, central-repeat, and C-terminal regions of CSP, and positive responders had greater antibody breadth compared to those who were negative for complement-fixing antibodies (p<0.05). Using rabbit vaccinations as a model, we confirmed that IgG specific to the central-repeat and non-repeat regions of CSP could effectively fix complement. However, vaccination with near full length CSP in rabbits poorly induced antibodies to the N-terminal region compared to naturally-acquired immunity in humans. Poor induction of N-terminal antibodies was also observed in a vaccination study performed in mice. IgG and IgM to all three regions of CSP play a role in mediating complement-fixation, which has important implications for malaria vaccine development.

Small ruminants affected by brucellosis, caused mainly by Brucella melitensis and B. ovis, suffer reproductive disorders, leading to significant economic losses worldwide. Vaccination is an essential tool to prevent the disease in ovine and caprine livestock, but the only vaccine recommended to date is B. melitensis Rev1, which in sheep is only safe for use in lambs aged 3–4 months. This restriction poses considerable practical challenges for the implementation of Rev1 in countries with endemic brucellosis and/or limited resources, where there is a need for mass vaccination with a safe vaccine to control the disease in both animals and humans. We recently developed a B. melitensis strain Rev1Δwzm showing superior vaccine properties in mice and safety in pregnant ewes. Here, we report that Rev1Δwzm (i) is safe in young and adult sheep, both male and female; (ii) induces a transient serological response in the Rose Bengal test in ≤50 % of sheep, confirmed to some extent by the complement fixation test, and a stronger, more persistent anti- rough-LPS response; and (iii) protects rams against a B. ovis challenge 25 weeks after vaccination. To resolve the problem of serological interference, the use of green fluorescent protein tagging strategy allowed us to identify vaccinated sheep with only a single inoculation. These results, together with the previously reported safety in pregnant ewes, position Rev1Δwzm as a firm vaccine candidate and a promising alternative to Rev1. Further experiments are warranted to assess its efficacy against B. melitensis in pregnant ewes.

Equine trypanosomosis remains an important veterinary concern in regions where horses play a significant economic and cultural role. In Kazakhstan, comprehensive nationwide data on the seroepidemiological status of equine trypanosomes are limited. The aim of this study was to assess the serological distribution of equine trypanosomosis across all administrative regions of Kazakhstan using complement fixation testing (CFT). A total of 6065 equine serum samples were collected from seventeen regions between 2023 and 2025. Antibodies against members of the Trypanozoon subgenus were detected using a WOAH-recommended CFT protocol. Overall seropositivity was 4.73%, with substantial regional variation ranging from 0% to 16.52%. Statistically significant differences in seroprevalence were observed between regions (p < 0.001), and mixed-effects modelling indicated considerable regional clustering. PCR testing of seropositive samples did not confirm the presence of Trypanosoma equiperdum, while one sample tested positive for Trypanosoma evansi. These findings suggest that CFT seropositivity reflects exposure to equine trypanosomes rather than confirmed dourine infection. Given the inability of CFT to reliably distinguish between T. equiperdum and T. evansi, species-level attribution remains uncertain. This study provides the first nationwide overview of serological reactivity to equine trypanosomes in Kazakhstan. The results highlight regional heterogeneity in antibody detection and underscore the need for expanded molecular surveillance and improved species-specific diagnostic tools to clarify the epidemiological status of equine trypanosomosis in the country.

Pneumonia is a life threatening public health concern particularly due to multidrug resistant (MDR) bacterial pathogens. The rising threat of these resistant bacterial strains has exacerbated the challenge of treating bacterial pneumonia, emphasizing the urgent need of alternative therapeutic strategies such as vaccine development by targeting combined localized MDR bacterial pneumonia pathogens. In this study, clinical samples of bacterial pneumonia pathogens were collected from tertiary care hospitals of Lahore, Punjab, Pakistan. Strains were isolated and characterized on biochemical and molecular basis. The localized vaccines, including inactivated whole-cell vaccines, bivalent vaccine (KP + SP), combined vaccine (SP + LPS) and lipopolysaccharide (LPS)-based vaccines by targeting the most dominant bacterial pathogens K. pneumoniae and S. pneumoniae were prepared. The experimental trial was conducted on 7th, 14th, 48th, 60th and 90th days interval. Mice were immunized and immune responses were assessed using complement fixation test (CFT). Mice were challenged with a lethal dose (LD 50 ) of pathogenic strain of K. pneumoniae and S. pneumoniae . Then, survival rate of each group of mice were monitored over time. indicated that the mean antibody titers peaked on 48th day for all vaccine groups, followed by a decline by 90th day of post vaccination. Among all vaccine groups, the bivalent vaccine (KP + SP) exhibited the most significant results ( p  < 0.05), with 98–99% survival rate. It may be concluded from this study that bivalent vaccine (KP + SP) significantly enhanced the protective humoral immune response against MDR bacterial pneumonia pathogens. And, LPS have potential immunogenic components for future vaccine development.

Defining correlates of immunity by comprehensively interrogating the extensive biological diversity in naturally or experimentally protected subjects may provide insights critical for guiding the development of effective vaccines and antibody‐based therapies. We report advances in a humoral immunoprofiling approach and its application to elucidate hallmarks of effective HIV‐1 viral control. Systematic serological analysis for a cohort of HIV‐infected subjects with varying viral control was conducted using both a high‐resolution, high‐throughput biophysical antibody profiling approach, providing unbiased dissection of the humoral response, along with functional antibody assays, characterizing antibody‐directed effector functions such as complement fixation and phagocytosis that are central to protective immunity. Profiles of subjects with varying viral control were computationally analyzed and modeled in order to deconvolute relationships among IgG Fab properties, Fc characteristics, and effector functions and to identify humoral correlates of potent antiviral antibody‐directed effector activity and effective viral suppression. The resulting models reveal multifaceted and coordinated contributions of polyclonal antibodies to diverse antiviral responses, and suggest key biophysical features predictive of viral control. Synopsis Interrogation and systematic analysis of the humoral immune response define correlates of antibody effector function and humoral responses associated with spontaneous HIV‐1 suppression, indicating new metrics, which may be relevant for HIV vaccine trials. High resolution profiling of antibody features and effector functions is used to evaluate immune responses in HIV infection. Humoral responses associated with spontaneous viral suppression are modeled. Features of antibodies associated with potent effector function are defined. The identified antibody markers of HIV viral suppression and potent effector function may be useful for benchmarking HIV vaccines. Graphical Abstract Interrogation and systematic analysis of the humoral immune response define correlates of antibody effector function and humoral responses associated with spontaneous HIV‐1 suppression, indicating new metrics, which may be relevant for HIV vaccine trials.

Theileria equi (Laveran 1901) and Babesia caballi (Nuttall and Strickland 1910) are the causative agents of Equine Piroplasmosis (EP), a severe and problematic disease compromising international movement of horses. Infected horses usually become asymptomatic carriers and, for this reason, their movement across borders may become restricted. The aim of this study was to assess the seroprevalence of EP in Southern France and to evaluate risk factors associated with these parasites. In 2002, we performed a complement fixation test (CF) with blood samples from 443 horses stabled at 95 different farms located in the region of Camargue. Two epidemiological questionnaires have been used: one for each single horse (individual and management factors) and one for each place where horses were sampled (environment, presence of other species, etc.) to identify risk factors for seropositivity. T. equi and B. caballi had a seroprevalence of 58 % and 12.9 %, respectively. For T. equi, sex, age, activity, management, and living with or near cattle were identified as risk factors, while for B. caballi, only living in wetlands was recognized as a risk factor in the bivariate analysis. In the multivariate analysis, the best model for T. equi included as variables age, breed, and deworming, while the best model for B. caballi included the type of housing during day and the contact with cows.

Dourine is a sexually transmitted parasitic disease affecting equids. Its causative agent is referred to as Trypanosoma equiperdum and the prescribed serodiagnosis method is the complement fixation test (CFT). In the context of our European Reference Laboratory mandate for equine diseases (excluding African horse sickness), we organised dourine CFT inter-laboratory proficiency tests (ILPTs) in 2015, 2018 and 2022 to evaluate the performance of the European Union network of National Reference Laboratories (NRLs) for dourine. ILPT panels were composed of horse sera with or without antibodies against Trypanosoma spp. originating from non-infected, immunised or experimentally infected horses. Twenty-two NRLs participated in at least one of the three sessions. In 2015, 2018 and 2022, the percentage of laboratories obtaining 100% of the expected results was 57, 90 and 80, respectively. These dourine CFT ILPTs showed the benefits of standardising the method’s detection limit and underlined the constant need to evaluate NRLs to improve the network’s performance. These results also argue in favour of the need for a representative bio-bank to improve the representativeness of ILPT samples and to allow the adoption of alternative serological methods for international surveillance of dourine.

Brucellosis is one of the most important zoonotic diseases in Greece, causing a significant burden on both human and animal vitality as well as economic loss. The present study was conducted from 2015 to 2022 on 711,415 serum samples by determining the seroepidemiology of Brucellosis among livestock in 24 geographical areas in Greece using the Rose Bengal Test (RBT) and the complement fixation test (CFT) and further performing genetic analysis of Brucella spp. by species-specific real-time PCR and MLVA Brucella analysis. A total of 3086 serum samples from goats, sheep, and cattle showed positive results using the RBT and CFT, and only strongly positive samples (n = 800) were preserved in the Βlood Bank of the Veterinary Laboratory of Brucellosis. From these, 212 sera samples were randomly selected for molecular and genetic analysis. The results indicated that the incidence rate of Brucellosis is higher in cattle herds in comparison with other animal species. Overall, 48 samples tested positive by real-time PCR, of which forty-seven of them were B. abortus and one was B. melitensis. Genetic analysis of two B. abortus samples revealed a common pattern, indicating two Bruce04, two Bruce18, four Bruce07, two Bruce09, three Bruce16, and four Bruce30 for both samples, which, interestingly, were not identical with the known genotypes in the public MLVA Brucella database. Our findings substantiate that animal Brucellosis remains a health issue in Greece, with a stable but apparent incidence rate, and further investigation is needed to fully characterize the newly identified Brucella strains in Greece.