Seroprevalence study reveals pertussis underreporting in Brazil and calls for adolescent/young adult boosting: mouse model demonstrates immunity restoration.

Background: Pertussis continues to pose a significant threat despite the availability of effective vaccines. The challenge lies in the vulnerability of infants who have not yet completed their vaccination schedule and in adolescents and adults becoming potential disease carriers.

Methods: We evaluated the seroprevalence of pertussis immunity in a cohort of 1,500 healthy Brazilian volunteers.

Comparison Between Simple Batch and Fed-Batch Bioreactor Cultivation of Recombinant BCG.

: Tuberculosis continues to be a significant global health concern, causing 1.3 million deaths in 2022, particularly affecting children under 5 years old. The Bacillus Calmette-Guérin (BCG) vaccine, developed in 1921, remains the primary defense against tuberculosis but requires modernized production methods.

Chromosomal Type II Toxin-Antitoxin Systems May Enhance Bacterial Fitness of a Hybrid Pathogenic Strain Under Stress Conditions.

The functions of bacterial plasmid-encoded toxin-antitoxin (TA) systems are unambiguous in the sense of controlling cells that fail to inherit a plasmid copy. However, its role in chromosomal copies is contradictory, including stress-response-promoting fitness and antibiotic treatment survival. A hybrid pathogenic strain may have the ability to colonize distinct host niches, facing contrasting stress environments.

Co-expression gene module analysis in response to attenuated cercaria vaccine reveals a critical role for NK cells in protection against Schistosoma mansoni.

Background: Despite decades of research, an effective schistosomiasis vaccine remains elusive. The radiation-attenuated (RA) cercarial vaccine remains the best model for eliciting high levels of protection. We have recently explored this model in mice to identify potentially protective pathways by examining gene expression patterns in peripheral blood mononuclear cells (PBMC).

Antigenic epitope targets of rhesus macaques self-curing from infection.

The self-cure of rhesus macaques from a schistosome infection and their subsequent strong immunity to a cercarial challenge should provide novel insights into the way these parasites can be eliminated by immunological attack. High-density arrays comprising overlapping 15-mer peptides from target proteins printed on glass slides can be used to screen sera from host species to determine antibody reactivity at the single epitope level. Careful selection of proteins, based on compositional studies, is crucial to encompass only those exposed on or secreted from the intra-mammalian stages and is intended to focus the analysis solely on targets mediating protection.

Schistosoma mansoni vaccine candidates identified by unbiased phage display screening in self-cured rhesus macaques.

Schistosomiasis, a challenging neglected tropical disease, affects millions of people worldwide. Developing a prophylactic vaccine against Schistosoma mansoni has been hindered by the parasite's biological complexity. In this study, we utilized the innovative phage-display immunoprecipitation followed by a sequencing approach (PhIP-Seq) to screen the immune response of 10 infected rhesus macaques during self-cure and challenge-resistant phases, identifying vaccine candidates.

Fusion of PspA to detoxified pneumolysin enhances pneumococcal vaccine coverage.

Despite the implementation of conjugate vaccines in several countries, S. pneumoniae continues to pose a great burden worldwide, causing around 1 million annual deaths. Pneumococcal proteins have long been investigated as serotype-independent vaccines against this pathogen, with promising results.

Recombinant BCG expressing the LTAK63 adjuvant increased memory T cells and induced long-lasting protection against challenge in mice.

Vaccine-induced protection against is usually ascribed to the induction of Th1, Th17, and CD8 T cells. However, protective immune responses should also involve other immune cell subsets, such as memory T cells. We have previously shown improved protection against challenge using the rBCG-LTAK63 vaccine (a recombinant BCG strain expressing the LTAK63 adjuvant, a genetically detoxified derivative of the A subunit from heat-labile toxin).

Recombinant Bacillus Calmette-Guérin Expressing SARS-CoV-2 Chimeric Protein Protects K18-hACE2 Mice against Viral Challenge.

COVID-19 has accounted for more than 6 million deaths worldwide. Bacillus Calmette-Guérin (BCG), the existing tuberculosis vaccine, is known to induce heterologous effects over other infections due to trained immunity and has been proposed to be a potential strategy against SARS-CoV-2 infection. In this report, we constructed a recombinant BCG (rBCG) expressing domains of the SARS-CoV-2 nucleocapsid and spike proteins (termed rBCG-ChD6), recognized as major candidates for vaccine development.

Peptide linker increased the stability of pneumococcal fusion protein vaccine candidate.

is a bacterial pathogen exclusive to humans, responsible for respiratory and systemic diseases. Pneumococcal protein vaccines have been proposed as serotype-independent alternatives to currently used conjugated polysaccharide vaccines, which have presented limitations regarding their coverage. Previously in our group, pneumococcal surface protein A (PspA) and detoxified pneumolysin (PdT) were genetically fused and the hybrid protein protected mice against pneumococcal challenge, offered higher cross-protection against different strains and showed greater opsonophagocytosis rate than co-administered proteins.

A fusion protein comprising pneumococcal surface protein A and a pneumolysin derivate confers protection in a murine model of pneumococcal pneumonia.

PspA and pneumolysin are two important vaccine candidates, able to elicit protection in different models of pneumococcal infection. The high immunogenic potential of PspA, combined with a possible adjuvant effect of pneumolysin derivatives (due to their ability to interact with TLR-4) could greatly improve the immunogenicity and coverage of a protein-based pneumococcal vaccine. A chimeric protein including the N-terminal region of PspA in fusion with the pneumolysin derivative, PlD1, has been shown to induce high antibody levels against each protein, and protect mice against invasive challenge.

100 Years of BCG Immunization: Past, Present, and Future.

The 100th anniversary of the introduction of Bacille-Calmette-Guérin (BCG) as a tuberculosis (TB) vaccine is an occasion warranting further investigation of the early attempts which culminated in the introduction of BCG as a TB vaccine, as well as of subsequent recognition of failures, new findings that broaden its applications, outstanding questions, and approaches towards the development of novel vaccine candidates [...

Recombinant BCG expressing the LTAK63 adjuvant improves a short-term chemotherapy schedule in the control of tuberculosis in mice.

Tuberculosis (TB) is one of the deadliest infectious diseases around the world. Prevention is based on the prophylactic use of BCG vaccine, effective in infants but as protection wanes with time, adults are less protected. Additionally, chemotherapy requires the use of many antibiotics for several months to be effective.

Immune response induced in mice by a hybrid rPotD-PdT pneumococcal protein.

Streptococcus pneumoniae is a human pathogen that colonizes the naso and/or oropharynx and can cause otitis, pneumonia, bacteremia and meningitis. To broaden the protection against pneumococcus, several pneumococcal proteins have been investigated as vaccine candidates. In this study we analyzed the immunological response induced by mouse subcutaneous immunization with a fusion of the Polyamine transport protein D (PotD) and a pneumolysin derivative (PdT), resulting in a hybrid rPotD-PdT protein.

Recombinant BCG-LTAK63 Vaccine Candidate for Tuberculosis Induces an Inflammatory Profile in Human Macrophages.

Tuberculosis (TB) is one of the top 10 leading causes of death worldwide. The recombinant BCG strain expressing the genetically detoxified A subunit of the thermolabile toxin from (LTAK63) adjuvant (rBCG-LTAK63) has previously been shown to confer superior protection and immunogenicity compared to BCG in a murine TB infection model. To further investigate the immunological mechanisms induced by rBCG-LTAK63, we evaluated the immune responses induced by rBCG-LTAK63, BCG, and () H37Rv strains in experimental infections of primary human M1 and M2 macrophages at the transcriptomic and cytokine secretion levels.

CRISPR/Cas9 Approach to Generate an Auxotrophic BCG Strain for Unmarked Expression of LTAK63 Adjuvant: A Tuberculosis Vaccine Candidate.

Tuberculosis is one of the deadliest infectious diseases and a huge healthcare burden in many countries. New vaccines, including recombinant BCG-based candidates, are currently under evaluation in clinical trials. Our group previously showed that a recombinant BCG expressing LTAK63 (rBCG-LTAK63), a genetically detoxified subunit A of heat-labile toxin (LT) from , induces improved protection against () in mouse models.

Recombinant BCG Expressing the Subunit 1 of Pertussis Toxin Induces Innate Immune Memory and Confers Protection against Non-Related Pathogens.

BCG has shown the ability to induce protection against unrelated pathogens, which likely depends on an immune mechanism known as innate immune memory or trained immunity. In this study, we evaluated the induction of innate memory by a recombinant BCG strain expressing the genetically detoxified S1 subunit of the pertussis toxin (rBCG-S1PT). In vitro pre-exposure of naïve murine macrophages to rBCG-S1PT increased their innate/inflammatory response (IL-6, TNF-α, and IL-10) to a subsequent challenge with unrelated pathogens, as compared to pre-exposure to wild-type BCG.

Robust Immune Response Induced by TSP-2 Antigen Coupled to Bacterial Outer Membrane Vesicles.

Purpose: The use of adjuvants can significantly strengthen a vaccine's efficacy. We sought to explore the immunization efficacy of bacterial outer membrane vesicles (OMVs) displaying the antigen, SmTSP-2, through a biotin-rhizavidin coupling approach. The rationale is to exploit the nanoparticulate structure and the adjuvant properties of OMVs to induce a robust antigen-specific immune response, in light of developing new vaccines against

Materials And Methods: OMVs were obtained from and conjugated with biotin.

Engineering a new vaccine platform for heterologous antigen delivery in live-attenuated .

Live vaccines are attractive vehicles for antigen delivery as a strategy to immunize against heterologous pathogens. The live vaccine MTBVAC is based on rational attenuation of with the objective of improving BCG protection against pulmonary tuberculosis. However, the development of recombinant mycobacteria as antigen-presenting microorganisms has been hindered due to their fastidious genetic manipulation.

Thirty years of recombinant BCG: new trends for a centenary vaccine.

: Global perception of the potential for Bacille Calmette-Guérin (BCG), and consequently recombinant BCG (rBCG), in a variety of prophylactic and therapeutic applications has been increasing. A century of information on BCG, and three decades of experience with rBCG, has generated solid knowledge in this field.: Here, we review the current state of knowledge of BCG and rBCG development.

Optimization of Expression and Purification of Schistosoma mansoni Antigens in Fusion with Rhizavidin.

Schistosomiasis causes significant morbidity and mortality. Vaccine efforts to date indicate the need to increase the immunogenicity of Schistosoma antigens. The multiple antigen-presenting system, whereby proteins are genetically fused to rhizavidin and affinity linked to biotinylated templates, enables the generation of robust immune responses.

Primary and Memory Response of Human Monocytes to Vaccines: Role of Nanoparticulate Antigens in Inducing Innate Memory.

Innate immune cells such as monocytes and macrophages are activated in response to microbial and other challenges and mount an inflammatory defensive response. Exposed cells develop the so-called innate memory, which allows them to react differently to a subsequent challenge, aiming at better protection. In this study, using human primary monocytes in vitro, we have assessed the memory-inducing capacity of two antigenic molecules of in soluble form compared to the same molecules coupled to outer membrane vesicles of .