October 2, 2023

A sample size of ~?230 adults per vaccination group provided at least 90% power to demonstrate non-inferiority and superiority for at least one of the PCV15 formulations based on OPA

A sample size of ~?230 adults per vaccination group provided at least 90% power to demonstrate non-inferiority and superiority for at least one of the PCV15 formulations based on OPA. in recipients of either PCV15 formulation were non-inferior (?2-fold margin) to those measured in recipients of PCV13 for shared serotypes and superior ( Etamivan ?1.0-fold difference) for serotypes unique to PCV15. Formulation B generally induced higher immune responses than Formulation A. Conclusion: In healthy adults ?50?years of age, both new formulations of PCV15 displayed acceptable security profiles and induced serotype-specific immune responses comparable to PCV13. strong class=”kwd-title” Keywords: pneumococcal conjugate vaccine, security, immunogenicity Introduction Pneumococcal disease (PD) is usually associated with significant morbidity and mortality worldwide. Children ?5?years of age, older adults ?65?years of age, and individuals of any age with certain medical conditions (i.e., malignancy, chronic heart disease, chronic Etamivan lung disease, and diabetes mellitus) are at increased risk for pneumococcal disease.1,2 High incidence of disease in older adults is due to immune senescence and physiological changes in the respiratory system associated with aging.3 Invasive pneumococcal disease (IPD) includes disease with high degree of invasiveness such as meningitis, bacteremia/sepsis, and bacteremic pneumonia. Non-invasive disease includes sinusitis, otitis media, and non-bacteremic pneumonia.4 Incidence of pneumococcal pneumonia without bacteremia is difficult to estimate due to limited use in clinical practice of confirmatory laboratory test despite recent development of new urinary tests aimed at detecting all or serotype-specific cases of non-bacteremic pneumococcal pneumonia.5C7 Several pneumococcal polysaccharide vaccines (PPVs) containing capsular polysaccharides from 6 to 23 serotypes have been developed since the 1970s. Currently, only the 23-valent pneumococcal polysaccharide vaccine (PPV23) is usually licensed in many countries worldwide. Effectiveness of PPV23 against IPD in immunocompetent adults has generally ranged from 56-to-81%, but is lower in immunocompromised individuals.8 Additionally, the vaccine was found to be ineffective in children ?2?years of age due to the immaturity of their immune system. Efficacy of PPV23 against pneumococcal pneumonia was exhibited in several studies but rates varied between studies.9C14 Although underused, Etamivan PPVs were shown to be efficacious and cost-effective against pneumococcal disease.15C17 In order to improve vaccine effectiveness in children, several pneumococcal conjugate vaccines (PCV7 [Prevnar?, Pfizer, Philadelphia], PCV10 [Synflorix?, GlaxoSmithKline, Rixensart, Belgium], and PCV13 [Prevnar 13?, Pfizer, Philadelphia, PA]) have been licensed since 2000. Efficacy of PCV7 against IPD was exhibited in several pediatric clinical trials18-20 and effectiveness of both PCV10 and PCV13 against IPD and otitis media has been observed in children ?5?years of age.21C24 Recently, a placebo-controlled study (CAPiTA) showed PCV13 to be 45.6% efficacious in preventing first episode of vaccine-type (VT) pneumococcal pneumonia and 75% against VT-IPD but did not improve overall survival of vaccinated adults ?65?years of age compared to placebo.7 Based on CAPiTA results, sequential dosing regimen of PCV13 followed by PPV23 administered 1?12 months later was adopted in the U.S. for adults ?65?years of age but usage of PCV13 in adults remains undecided in most countries with established child years PCV programs. Widespread use of these vaccines has led to significant reduction in nasopharyngeal carriage, IPD, and pneumococcal pneumonia Etamivan in the population targeted by vaccination but also in other age groups (herd protection). For all those age groups, greater impact has been observed in disease caused by vaccine serotypes whereas cases of IPD caused by non-vaccine serotypes have increased over time.25C31 Interestingly, disease caused by serotypes not CTMP included in newly licensed vaccines, including 22F and 33F, also increased in recent years.32C34 Vaccine impact was observed for both IPD and pneumococcal pneumonia.32C38 A 15-valent pneumococcal conjugate vaccine (PCV15) comprised of serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, and 33F has the potential to address important medical and public health requires by providing broader coverage for leading serotypes associated with pneumococcal disease worldwide.39 In comparison to PCV13, the 2 2 serotypes unique to PCV15 (22F and 33F) are among leading serotypes causing IPD in children and adults following widespread use of PCV13 in children in many countries, likely due to their invasiveness capacity.25,28,32C34 By 2013 in the US, residual IPD caused by serotype 22F among children ?5?years and adults ?18?years were 11% and Etamivan 13%, respectively while serotype 33F.