Safety, reactogenicity, and immunogenicity of a novel 24-valent pneumococcal vaccine candidate in healthy, pneumococcal vaccine-naïve Japanese adults: A phase 1 randomized dose-escalation trial.

Background: The burden of pneumococcal diseases remains high in Japan. Pn-MAPS24v is a novel MAPS-based vaccine containing complexes of 24 serotype-specific polysaccharides (PS), non-covalently coupled with fusion protein 1 (CP1). This study evaluated the safety and immunogenicity of different dose levels of Pn-MAPS24v, administered in Japanese adults either subcutaneously (SC) or intramuscularly (IM).

Evaluation of a Quadrivalent Serotype 2a, 3a, 6, and O-Specific Polysaccharide and IpaB MAPS Vaccine.

Background: Shigellosis is the leading cause of diarrheal deaths worldwide and is particularly dangerous in children under 5 years of age in low- and middle-income countries. Additionally, the rise in antibiotic resistance has highlighted the need for an effective vaccine. Previously, we have used the Multiple Antigen-Presenting System (MAPS) technology to generate monovalent and quadrivalent MAPS vaccines that induce functional antibodies against components.

WNT5A is a putative epi-driver of prostate cancer metastasis to the bone.

Background: Current diagnostic tools are unable to distinguish low-grade indolent prostate cancer (PrCa) from that with a propensity to become metastatic and/or lethal. Recent evidence suggests that reprogramming of the transcriptome may drive the metastatic phenotype, and that this reprogramming is controlled, at least in part, by epigenetic changes to the DNA of cancer cells, including methylation. These changes, referred to as 'epigenetic drivers,' have previously been associated with cancer cell survival.

Household Transmission Dynamics of Asymptomatic SARS-CoV-2-Infected Children: A Multinational, Controlled Case-Ascertained Prospective Study.

Background: Asymptomatic SARS-CoV-2 infection in children is highly prevalent but its acute and chronic implications have been minimally described.

Methods: In this controlled case-ascertained household transmission study, we recruited asymptomatic children <18 years with SARS-CoV-2 nucleic acid testing performed at 12 tertiary care pediatric institutions in Canada and the United States. We attempted to recruit all test-positive children and 1 to 3 test-negative, site-matched controls.

Safety, tolerability and immunogenicity of a novel 24-valent pneumococcal vaccine in toddlers: A phase 1 randomized controlled trial.

Background: Pneumococcal conjugate vaccines (PCVs) significantly reduced pneumococcal disease burden. Nevertheless, alternative approaches for controlling more serotypes are needed. Here, the safety, tolerability, and immunogenicity of a 24-valent (1/2/3/4/5/6A/6B/7F/8/9N/9V/10A/11A/12F/14/15B/17F/18C/19A/19F/20B/22F/23F/33F) pneumococcal vaccine based on Multiple Antigen-Presenting System (MAPS) technology (Pn-MAPS24v) was assessed in toddlers.

Immunization with a whole cell vaccine reduces pneumococcal nasopharyngeal density and shedding, and middle ear infection in mice.

Pneumococcal Conjugate Vaccines (PCVs) have substantially reduced the burden of disease caused by Streptococcus pneumoniae (the pneumococcus). However, protection is limited to vaccine serotypes, and when administered to children who are colonized with pneumococci at the time of vaccination, immune responses to the vaccine are blunted. Here, we investigate the potential of a killed whole cell pneumococcal vaccine (WCV) to reduce existing pneumococcal carriage and mucosal disease when given therapeutically to infant mice colonized with pneumococci.

Multiple antigen presenting system (MAPS): state of the art and potential applications.

Introduction: Technological innovations have been instrumental in advancing vaccine design and protective benefit. Improvements in the safety, tolerability, and efficacy/effectiveness profiles have profoundly reduced vaccine-preventable global disease morbidity and mortality. Here we present an original vaccine platform, the Multiple Antigen Presenting System (MAPS), that relies on high-affinity interactions between a biotinylated polysaccharide (PS) and rhizavidin-fused pathogen-specific proteins.

Induction of Broad Immunity against Invasive Salmonella Disease by a Quadrivalent Combination Salmonella MAPS Vaccine Targeting Salmonella Enterica Serovars Typhimurium, Enteritidis, Typhi, and Paratyphi A.

Bloodstream infections in low- and middle-income countries (LMICs) are most frequently attributed to invasive Salmonella disease caused by four primary serovars of enterica: Typhi, Paratyphi A, Typhimurium, and Enteritidis. We showed previously that a bivalent vaccine targeting . Typhi and .

Impact of SARS-CoV-2 Infection on the Association Between Laboratory Tests and Severe Outcomes Among Hospitalized Children.

Background: To assist clinicians with identifying children at risk of severe outcomes, we assessed the association between laboratory findings and severe outcomes among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected children and determined if SARS-CoV-2 test result status modified the associations.

Methods: We conducted a cross-sectional analysis of participants tested for SARS-CoV-2 infection in 41 pediatric emergency departments in 10 countries. Participants were hospitalized, had laboratory testing performed, and completed 14-day follow-up.

Therapeutic Targeting of Inflammation and Virus Simultaneously Ameliorates Influenza Pneumonia and Protects from Morbidity and Mortality.

Influenza pneumonia is a severe complication caused by inflammation of the lungs following infection with seasonal and pandemic strains of influenza A virus (IAV), that can result in lung pathology, respiratory failure, and death. There is currently no treatment for severe disease and pneumonia caused by IAV. Antivirals are available but are only effective if treatment is initiated within 48 h of onset of symptoms.

A MAPS Vaccine Induces Multipronged Systemic and Tissue-Resident Cellular Responses and Protects Mice against Mycobacterium tuberculosis.

Tuberculosis (TB) remains a leading cause of morbidity and mortality worldwide. To date, the mainstay of vaccination involves the use of Mycobacterium bovis bacillus Calmette-Guérin (BCG), a live-attenuated vaccine that confers protection against extrapulmonary disease in infants and children but not against lung disease. Thus, there is an urgent need for novel vaccines.

A Bivalent MAPS Vaccine Induces Protective Antibody Responses against Typhi and Paratyphi A.

Infections by Salmonella Typhi and Paratyphi A strain are still a major cause of morbidity and mortality in developing countries. Generation of antibodies against the Vi capsular polysaccharide of . Typhi via either pure polysaccharide or protein-polysaccharide conjugate is a very effective way to protect against .

Acute otitis media pneumococcal disease burden and nasopharyngeal colonization in children due to serotypes included and not included in current and new pneumococcal conjugate vaccines.

Introduction: Despite the introduction of effective pneumococcal conjugate vaccines (PCV), Streptococcus pneumoniae remains a major cause of acute otitis media (AOM) worldwide. New, higher valency vaccines that offer broader serotype coverage have been recently developed and others are in development. However, given the capsular serotypes expressed by pneumococci causing AOM, it is unclear to what extent differing or higher valency PCVs will provide additional protection.

Preclinical Immunogenicity and Efficacy of a Multiple Antigen-Presenting System (MAPS) SARS-CoV-2 Vaccine.

Despite the remarkable success of SARS-CoV-2 vaccines, the rise of variants, some of which are more resistant to the effects of vaccination, highlights the potential need for additional COVID-19 vaccines. We used the Multiple Antigen-Presenting System (MAPS) technology, in which proteins are presented on a polysaccharide polymer to induce antibody, Th1, Th17 and CD8+ T cell responses, to engineer a novel vaccine targeting SARS-CoV-2. This vaccine contains a fragment of the spike (S) protein receptor-binding domain (RBD) sequence of the original D614G strain and was used to immunize nonhuman primates (NHP) for assessment of immunological responses and protection against SARS-CoV-2 challenge.

Phase 1/2 study of a novel 24-valent pneumococcal vaccine in healthy adults aged 18 to 64 years and in older adults aged 65 to 85 years.

Background: Pneumococcal diseases remain prevalent despite available polysaccharide and conjugate vaccines. This phase 1/2 study evaluated safety/tolerability and immunogenicity of a novel 24-valent pneumococcal vaccine (ASP3772) based on high-affinity complexing of proteins and polysaccharides.

Methods: Pneumococcal vaccine-naïve adults aged 18-85 years were randomized to receive either ASP3772 or PCV13 (13-valent conjugate vaccine).

Targeted Transcriptomic Screen of Pneumococcal Genes Expressed during Murine and Human Infection.

The advent of pneumococcal conjugate vaccines led to the near disappearance of most of the included serotypes in high-income settings but also the rise of nonvaccine-type colonization and disease. Alternative strategies, using genetically conserved proteins as antigens, have been evaluated preclinically and clinically for years, so far unsuccessfully. One possible explanation for the failure of these efforts is that the choice of antigens may not have been sufficiently guided by an understanding of the gene expression pattern in the context of infection.

Antibody Seronegativity in COVID-19 RT-PCR-Positive Children.

This substudy of a prospective case-ascertained household transmission study investigated severe acute respiratory syndrome coronavirus 2 reverse transcription polymerase chain reaction-positive individuals without antibody development and factors associated with nonseroconversion. Approximately 1 of 8 individuals with coronavirus disease 2019 did not seroconvert. Children, particularly the youngest, were approximately half as likely to seroconvert compared with adults.

Corticosteroids and Other Treatments Administered to Children Tested for SARS-CoV-2 Infection in Emergency Departments.

Objective: We sought to determine if corticosteroid administration is associated with a SARS-CoV-2 nucleic acid test-positive result and to describe therapies administered to SARS-CoV-2 infected children.

Methods: We collected cross-sectional data from participants recruited in 41 pediatric emergency departments (ED) in 10 countries between March 2020 and June 2021. Participants were <18 years old, had signs or symptoms of, or risk factors for acute SARS-CoV-2 infection, and had nucleic acid testing performed.