Wendy Watson

Immunogenicity and Safety of 13-Valent Pneumococcal Conjugate Vaccine in HIV-Infected Adults Previously Vaccinated With Pneumococcal Polysaccharide Vaccine

BACKGROUND Persons with human immunodeficiency virus (HIV) infection are at increased risk of pneumococcal disease. We evaluated the safety and immunogenicity of 13-valent pneumococcal conjugate vaccine (PCV13) in this population. METHODS HIV-infected persons ≥ 18 years of age who were previously vaccinated with ≥ 1 dose of 23-valent pneumococcal polysaccharide vaccine (PPSV23) and had CD4 cell counts ≥ 200 cells/mm(3) and HIV viral loads <50 000 copies/mL were enrolled in this 3-dose PCV13 open-label study. RESULTS A total of 329 subjects received ≥ 1 dose, and 279 received 3 doses administered at 6-month intervals. Increases in anticapsular polysaccharide immunoglobulin G concentrations and opsonophagocytic antibody titers were demonstrated 1 month after each of the 3 doses of PCV13. Antibody levels were generally similar after each dose. The responses were similar whether subjects had previously received 1 or ≥ 2 doses of PPSV23. Pain at the injection-site was the most common local reaction. Severe injection site or systemic events were uncommon. CONCLUSIONS Vaccination with PCV13 induces anticapsular immunoglobulin G and opsonophagocytic antibody responses in HIV-infected adults with prior PPSV23 vaccination and CD4 cell counts ≥ 200 cells/mm(3). The observations support the use of PCV13 in this population. CLINICAL TRIALS REGISTRATION NCT00963235.

Preterm birth: Case definition & guidelines for data collection, analysis, and presentation of immunisation safety data

Preterm birth is commonly defined as any birth before 37 weeks completed weeks of gestation. An estimated 15 million infants are born preterm globally, disproportionately affecting low and middle income countries (LMIC). It contributes directly to estimated one million neonatal deaths annually and is a significant contributor to childhood morbidity. However, in many clinical settings, the information available to calculate completed weeks of gestation varies widely. Accurate dating of the last menstrual period (LMP), as well as access to clinical and ultrasonographic evaluation are important components of gestational age assessment antenatally. This case definition assign levels of confidence to categorisation of births as preterm, utilising assessment modalities which may be available across different settings. These are designed to enable systematic safety evaluation of vaccine clinical trials and post-implementation programmes of immunisations in pregnancy.

Pathways to preterm birth: Case definition and guidelines for data collection, analysis, and presentation of immunization safety data

Columbia University Medical Center, United States University of Washington, United States University of Witwatersrand, South Africa Global Alliance to Prevent Prematurity and Stillbirth (GAPPS), an Initiative of Seattle Childrens, United States University of Louisville, United States Research Triangle Institute, United States Optum Life Sciences, United States Philippine Society of Experimental and Clinical Pharmacology, Philippines Sanofi Pasteur, United States Pfizer, United States Global Healthcare Consulting, India

Immunogenicity and Safety of a 13-Valent Pneumococcal Conjugate Vaccine Coadministered with a Quadrivalent Influenza Vaccine in Adults 50 Years and Older Previously Vaccinated with 23-Valent Pneumococcal Polysaccharide Vaccine

LB-7. Immunogenicity and Safety of a 13-Valent Pneumococcal Conjugate Vaccine Coadministered with a Quadrivalent Influenza Vaccine in Adults 50 Years and Older Previously Vaccinated With 23-Valent Pneumococcal Polysaccharide Vaccine Roger Baxter, MD, FIDSA; H. Jackson Downey, MD; Scott D. Patterson, PhD; Vani Sundaraiyer, PhD; Wendy Watson, MD; Keri Clarke, MD; William C. Gruber, MD, FIDSA; Daniel A. Scott, MD; Allison Thompson, MD, FAAP; Beate SchmoeleThoma MD; Kaiser Permanente Vaccine Study Center, Oakland, California; Jacksonville Center for Clinical Research, Jacksonville, Florida; Pfizer Vaccine Research, Collegeville, Pennsylvania; inVentiv Health Clinical, LLC, Princeton, New Jersey; Pfizer Inc, Walton Oaks, United Kingdom; Pfizer Vaccine Research, Pearl River, New York; Pfizer Pharma GmbH, Berlin, Germany

Late onset of injection site reactions after vaccination with the 13-valent pneumococcal conjugate vaccine in adult study populations

ABSTRACT Injection site reactions (ISRs; redness, swelling and pain) commonly occur within 1–2 days after vaccination. After administration of toxoid vaccines including diphtheria toxoid, a later onset of ISRs has also been observed. As the serotype capsular polysaccharides in the 13-valent pneumococcal conjugate vaccine (PCV13) are conjugated to cross-reactive material 197 (CRM197), a nontoxic variant of diphtheria toxin, the onset of ISRs over 14 days was explored in 8 adult studies with 19 cohorts. Subjects received PCV13 with aluminum phosphate (AlPO4, n = 5667) or without AlPO4 (n = 304); 1097 subjects received 23-valent pneumococcal polysaccharide vaccine (PPSV23). Late ISRs with onset between days 6–14 were observed in 8/8 cohorts aged ≥65 years after PCV13 with AlPO4 (incidence across cohorts for redness, 2.3%-19.6%; swelling, 0.9%-10.8%; pain, 1.6%-10.0%) and in 1/1 cohort after PCV13 without AlPO4 (redness 10.5%; swelling 7.5%; pain 12.3%); and in 2/4 cohorts aged 50 to 64 years after PCV13 (redness 3.1%-4.8%; swelling 1.0%-3.2%; pain 3.7%-5%). Late ISRs were not generally observed in 1/1 cohort aged 18 to 49 years after PCV13; in 2/2 cohorts aged ≥53 years after PCV13 revaccination; and in 3/3 cohorts aged ≥60 years who received PPSV23, which does not contain CRM197. Post hoc analysis demonstrated numerically higher pneumococcal immune responses in subgroups with late ISRs versus those without. In conclusion, causality of late ISRs is likely multifactorial, with age and the PCV13 carrier protein CRM197 potentially associated. AlPO4, a vaccine adjuvant, did not appear causally related. Observations do not affect the favorable risk-benefit profile of PCV13.

Coadministration of 13-valent pneumococcal conjugate and quadrivalent inactivated influenza vaccines in adults previously immunized with polysaccharide pneumococcal vaccine 23: a randomized clinical trial

ABSTRACT Immune responses to 13-valent pneumococcal conjugate vaccine (PCV13) and quadrivalent inactivated influenza vaccine (QIV) in older adults may vary with coadministration and previous pneumococcal polysaccharide vaccination. This study assessed safety and noninferiority of immune responses to coadministered PCV13 and QIV compared with each vaccine given alone. Adults ≥50 years old preimmunized with ≥1 dose of 23-valent pneumococcal polysaccharide vaccine (PPSV23) ≥1 year before enrollment were randomized 1:1 to receive PCV13+QIV then placebo 1 month later or placebo+QIV then PCV13 1 month later. Administration of PCV13 and placebo was blinded; QIV was administered open-label. Pneumococcal serotype-specific opsonophagocytic activity (OPA) geometric mean titers (GMTs) 1 month after PCV13, and influenza hemagglutination inhibition assay GMTs 1 month after QIV were measured. Prespecified noninferiority was demonstrated by a lower bound of the 2-sided 95% CI for geometric mean ratios >0.5. Safety endpoints included proportions of subjects with adverse and serious adverse events. Of 882 randomized subjects, 846 comprised the evaluable immunogenicity population. Immune responses to all 13 pneumococcal serotypes and all 4 influenza strains 1 month after PCV13+QIV were noninferior to responses 1 month after each vaccine given alone. No safety concerns were identified. Immune responses to coadministered PCV13 and QIV were noninferior to responses after each vaccine given alone, although generally lower for coadministered PCV13. PCV13 and QIV can be administered concomitantly to adults ≥50 years of age preimmunized with PPSV23.