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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.

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.

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.

Brucellosis, a contagious zoonotic bacterial infection affecting livestock and wildlife, is primarily caused by Brucella abortus, globally. However, in South Africa, the true prevalence of bovine brucellosis remains unknown because of a lack of epidemiological data. Therefore, this study used diagnostic data to evaluate and determine the seropositivity of bovine brucellosis based on Rose Bengal test (RBT) screening and confirmation with complement fixation test (CFT) in Limpopo and Free State provinces between 2013 and 2022. The use and limitations of this data were also evaluated based on the bovine brucellosis scheme in South Africa. The study revealed the overall seropositivity of 4.2% (n = 8980/212 440) for bovine brucellosis based on RBT and CFT in series. In Limpopo province, the brucellosis seropositivity was slightly higher at 4.3% (n = 7488/173 011) compared to 3.8% (n = 1492/39 429) in Free State province. Analysis of brucellosis distribution over the study period indicated significant variation (p < 0.001) both between and within the provinces. Notably, the highest prevalence in Limpopo occurred during 2013–2017, whereas in Free State, peak prevalence was observed in 2013 and 2016. Challenges preventing an accurate reflection of the brucellosis seropositivity in these provinces for the period include a lack of data on vaccination history and herd status of the samples submitted, as well as the inability to match the CFT results from different laboratories, because some laboratories are only accredited to perform the RBT.ContributionInsights gained from retrospective studies such as this study can play crucial roles in shaping effective control and preventative measures against bovine brucellosis. Given the challenges in obtaining confirmatory test results, we suggest that brucellosis tests be conducted at a single central laboratory or that the government provides a central database where all laboratories can enter their data. Furthermore, information submitted to the laboratories must make herd and vaccine history compulsory for sample submission to ensure more accurate data.

Brucellosis is an infectious disease in domestic and wild animals with serious zoonotic and economic implication in humans, being more severe in developing countries. The disease is highly prevalent in cattle, camels, and small ruminants in pastoral and agro-pastoral areas in Africa. Here we have investigated the seroepidemiology of camel brucellosis in and around Dire Dawa, eastern Ethiopia, using a cross-sectional study design to determine the seroprevalence of the disease and to identify risk factors that would facilitate the transmission of zoonotic diseases to humans. This study involved testing 350 serum samples from camels and interviewing 120 livestock owners. The modified Rose Bengal plate test (mRBPT) and the complement fixation test (CFT) were used as screening and confirmatory tests, respectively. The overall sero-prevalence of camel brucellosis was found to be 8.3% and 2% using mRBPT and CFT tests, respectively. Among the risk factors assessed, only abortion and body condition disclosed a statistically significant difference p<0.05 with regard to the seropositivity of camel brucellosis. Camel brucellosis is prevalent in eastern Ethiopia and there is a need to execute well-organized disease control and prevention programs and exercise public health education to scale up awareness of the community towards the disease.

Surra, caused by ( ), is a significant vector-borne disease of camels that leads to substantial economic losses in affected regions. This study was conducted to determine the seroprevalence of surra among dromedary ( ) and Bactrian ( ) camels in Kazakhstan. A cross-sectional survey was carried out between January and May 2024 in the Mangystau, Kyzylorda, and Turkestan regions. A total of 2,773 camel serum samples (1,045 males and 1,728 females) were collected and tested using the complement fixation test (CFT) and the formol gel test (FGT). Chi-square tests were applied to assess differences across age groups, sexes, and regions. Antibodies against were detected in 113 camels (4.07%; 95% CI: 3.36-4.86) by CFT and in 276 camels (9.95%; 95% CI: 8.88-11.13) by FGT. Seroprevalence increased with age, with the highest rates observed in camels older than 12 years (5.93% by CFT and 26.27% by FGT). Females had significantly higher prevalence than males (CFT: 4.69% vs. 3.06%; FGT: 10.47% vs. 9.09%,  = 0.046). Regional variation was also noted, with the highest prevalence detected in Mangystau by FGT (65.0%). These findings confirm that camel surra is endemic in the surveyed regions of Kazakhstan. Both serological tests proved useful for large-scale screening of , and the FGT, due to its higher sensitivity, is recommended as the preferred tool for field surveillance.