After a dose for further testing was determined in a phase 1 study, a phase 2–3 trial was initiated in which two 10-μg doses of BNT162b2 were given 21 days apart to children 5 to 11 years of age. No ...serious adverse events were observed. High levels of neutralizing antibodies were induced, and vaccine efficacy 7 days or more after the second dose was 90.7%.
In March 2020, the World Health Organization (WHO) declared coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
, a pandemic. With ...rapidly accumulating numbers of cases and deaths reported globally
, a vaccine is urgently needed. Here we report the available safety, tolerability and immunogenicity data from an ongoing placebo-controlled, observer-blinded dose-escalation study (ClinicalTrials.gov identifier NCT04368728) among 45 healthy adults (18-55 years of age), who were randomized to receive 2 doses-separated by 21 days-of 10 μg, 30 μg or 100 μg of BNT162b1. BNT162b1 is a lipid-nanoparticle-formulated, nucleoside-modified mRNA vaccine that encodes the trimerized receptor-binding domain (RBD) of the spike glycoprotein of SARS-CoV-2. Local reactions and systemic events were dose-dependent, generally mild to moderate, and transient. A second vaccination with 100 μg was not administered because of the increased reactogenicity and a lack of meaningfully increased immunogenicity after a single dose compared with the 30-μg dose. RBD-binding IgG concentrations and SARS-CoV-2 neutralizing titres in sera increased with dose level and after a second dose. Geometric mean neutralizing titres reached 1.9-4.6-fold that of a panel of COVID-19 convalescent human sera, which were obtained at least 14 days after a positive SARS-CoV-2 PCR. These results support further evaluation of this mRNA vaccine candidate.
This randomized trial of the BNT162b2 vaccine involved 2260 adolescents 12 to 15 years of age. Similar levels of antibody to SARS-CoV-2 were elicited in the 12-to-15-year-old participants and in ...16-to-25-year-old participants in a parallel trial. Among participants with no evidence of previous infection, no cases of Covid-19 were diagnosed in vaccine recipients, as compared with 16 cases in placebo recipients.
Highlights • Pneumococcal conjugate vaccines elicit effective T cell dependent responses. • Conjugate and free polysaccharide vaccines were compared in older adults. • Conjugate responses were ...significantly greater for majority of serotypes. • Conjugate vaccine could provide enhanced immunity against pneumococcal disease.
Pneumococcal conjugate vaccines (PCVs) have significantly decreased pneumococcal disease worldwide; however, expanding serotype coverage may further reduce disease burden. A 20-valent PCV (PCV20) ...containing capsular polysaccharide conjugates of serotypes present in the 13-valent PCV (PCV13) and 7 new serotypes (8, 10A, 11A, 12F, 15B, 22F, and 33F) is currently in development. This phase 2 study evaluated safety, tolerability, and immunogenicity of PCV20 in adults without prior pneumococcal vaccination.
In this randomized, active-controlled, double-blinded trial, 444 adults 60 through 64 years of age were randomized to receive either a single dose of PCV20 followed 1 month later by saline placebo or a single dose of PCV13 followed 1 month later by 23-valent polysaccharide vaccine. Local injection site reactions, select systemic symptoms, and adverse events (AEs) were recorded. Immunogenicity was assessed by measuring serotype-specific opsonophagocytic activity (OPA) titers before and approximately 1 month after each vaccination.
Local reaction and systemic event rates were similar after vaccination with PCV20 or PCV13; no serious vaccine-related AEs were reported. In the PCV20 group, functional immune responses as measured by OPA were robust for all 20 serotypes included in the vaccine, with geometric mean fold rises from baseline ranging from 6.0 to 113.4.
PCV20 was well tolerated in adults 60 to 64 years of age, with a safety profile consistent with historical experience of PCVs in this age group. Substantial OPA responses were elicited against all serotypes. Results demonstrate the potential for PCV20 to expand pneumococcal disease protection.
NCT03313037.
The immunogenicity of a bivalent mRNA vaccine with both ancestral and omicron BA.1 sequences elicited higher neutralization titers against BA.1 than did the ancestral strain–specific vaccine.
Two doses 3 weeks apart of a lipid nanoparticle, nucleoside-modified RNA vaccine encoding a trimerized SARS-CoV-2 receptor–binding domain elicited high levels of antigen-binding and ...virus-neutralizing antibodies in adults 18 to 55 years and 65 to 85 years of age. Reactogenicity was moderate and transient. Large trials are ongoing.
In this double-blind, placebo-controlled trial involving more than 84,000 Dutch adults, the 13-valent pneumococcal conjugate vaccine was found to prevent pneumococcal disease but not the overall ...occurrence of community-acquired pneumonia.
Streptococcus pneumoniae
, a major cause of community-acquired pneumonia in the elderly, results in considerable morbidity and mortality.
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–
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Pneumococcal community-acquired pneumonia most commonly presents as nonbacteremic disease.
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Invasive pneumococcal disease, which involves infection of normally sterile sites, occurs in approximately 25% of cases.
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Immunologic protection against pneumococcal disease is mediated through opsonophagocytic antibodies directed against bacterial capsular polysaccharides that define the pneumococcal serotypes and serve as virulence factors.
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Vaccines composed of purified capsular polysaccharides, which have been available for more than 50 years, are not immunogenic in young children.
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–
8
Although some studies have shown that purified capsular polysaccharides . . .
AbstractIntroductionStreptococcus pneumoniae is a leading cause of bacteremia, bacterial pneumonia, and meningitis, and is associated with substantial morbidity and mortality, particularly in those ...under 2 years of age and those over 65 years of age. While significant progress against S. pneumoniae-related disease has been made as a result of the introduction of pneumococcal conjugate vaccines (PCV7, PCV10 and PCV13), there remains value in further expanding pneumococcal vaccine serotype coverage. Here we present the first report of a 20-valent pneumococcal conjugate vaccine (PCV20) containing capsular polysaccharide conjugates present in PCV13 as well as 7 new serotypes (8, 10A, 11A, 12F, 15B, 22F, and 33F) which are important contributors to pneumococcal disease. MethodsThis Phase I first-in-human study was a randomized, controlled, observer-blinded study with a two-arm parallel design to assess the safety, tolerability, and immunogenicity of PCV20 in adults. A total of 66 healthy adults 18–49 years of age with no history of pneumococcal vaccination were enrolled and randomized to receive a single dose of PCV20 or a licensed tetanus, diphtheria, acellular pertussis combination vaccine (Tdap) control. Local injection site reactions, select systemic symptoms, laboratory studies, and adverse events were assessed. Opsonophagocytic activity (OPA) titers and IgG concentrations were measured in sera collected prior to, and approximately one month (28–35 days) after vaccination. ResultsVaccination with PCV20 elicited substantial IgG and functional bactericidal immune responses as demonstrated by increases in IgG geometric mean concentrations (GMCs) and OPA geometric mean titers (GMTs) to the 20 vaccine serotypes. The overall safety profile of PCV20 was similar to Tdap, and generally consistent with that observed after PCV13 administration. ConclusionsVaccination with PCV20 was well tolerated and induced substantial functional (OPA) and IgG responses to all vaccine serotypes. There were no safety issues identified in this Phase 1 study, and the data supported further evaluation of PCV20.
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