William C Gruber

Pfizer · Vaccines Research Unit

Background/Objectives: Respiratory syncytial virus (RSV) is the leading cause of severe respiratory disease in infants worldwide. Maternal immunization to protect younger infants is supported by evidence that virus-neutralizing antibodies, which are efficiently transferred across the placenta from mother to fetus, are a primary immune mediator of p...

BACKGROUND AND OBJECTIVES The 20-valent pneumococcal conjugate vaccine (PCV20) was developed to expand protection for pneumococcal disease. It contains all 13-valent pneumococcal conjugate vaccine (PCV13) components plus conjugates for 7 additional serotypes. Our primary objective with this study was to evaluate PCV20 tolerability and safety. METH...

Background Clostridioides difficile infection (CDI) causes substantial mortality and healthcare burden. We assessed the detoxified toxin-A/B PF-06425090 vaccine for primary CDI prevention. Methods This phase 3 observer-blinded study randomized (1:1) ≥50-year-olds at increased CDI risk (N=17,535) to receive 3 PF-06425090 or placebo doses (0,1,6-mon...

Background With the future epidemiology and evolution of SARS-CoV-2 uncertain, use of safe and effective COVID-19 vaccines in pediatric populations remains important. Methods We report data from two open-label substudies of an ongoing phase 1/2/3 master study (NCT05543616) investigating safety and immunogenicity of a variant-adapted bivalent COVID...

Background Respiratory syncytial virus (RSV) causes substantial respiratory disease. Bivalent RSV prefusion F (RSVpreF) vaccine is licensed in ≥60-year-olds. RSVpreF was well-tolerated and immunogenic in a phase 1/2 study. We evaluated antibody persistence after initial vaccination and safety and immunogenicity after revaccination from this study....

Background The 20-valent pneumococcal conjugate vaccine (PCV20) was developed to extend pneumococcal disease protection beyond 13-valent PCV (PCV13). Methods This phase 3, double-blind study conducted in the United States/Puerto Rico evaluated PCV20 safety and immunogenicity. Healthy infants were randomized to receive a 4-dose series of PCV20 or P...

Rare myocarditis and pericarditis cases have occurred in coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) vaccine recipients. Troponin levels, a potential marker of myocardial injury, were assessed in healthy participants before and after BNT162b2 vaccination. Vaccine-experienced 12- to 30-year-olds in phase 3 crossover C4591031 Substudy B...

Background A 20-valent pneumococcal conjugate vaccine (PCV20), containing 13-valent PCV (PCV13) components and 7 additional polysaccharide conjugates, was developed to extend protection for pneumococcal disease. This phase 3 study assessed the safety and immunogenicity of PCV20 in children. Methods In this single-arm study, children (≥15 months–<1...

Background Global pediatric immunization programs with pneumococcal conjugate vaccines (PCVs) have reduced vaccine-type pneumococcal disease, but a substantial disease burden of non-PCV serotypes remains. Methods This phase 3, randomized (1:1), double-blind study evaluated safety and immunogenicity of 20-valent PCV (PCV20) relative to 13-valent PC...

Background Group A streptococci (GAS) are a major cause of pharyngitis in children. Recently, there were severe GAS outbreaks. The aims of this study were to assess pharyngeal colonization prevalence in healthy children, to assess different diagnostic definitions for GAS pharyngitis and to estimate incidence rates for these infections. Methods A 2...

Background Protection against contemporary SARS-CoV-2 variants requires sequence-adapted vaccines. Methods In this ongoing phase 2/3 trial, 12−17-year-olds (n=108), 18−55-year-olds (n=313), and >55-year-olds (n=306) who previously received 3 original BNT162b2 30-µg doses, received a fourth dose (second booster) of 30-µg bivalent original/Omicron-B...

Background The 20-valent pneumococcal conjugate vaccine (PCV20) was developed to expand protection against pneumococcal disease. PCV20 contains conjugates for serotype 6A, which is also in 13-valent PCV (PCV13) and appears to have had a clinical impact on 6C disease, and the additional serotype 15B. An exploratory assessment of cross-reactive funct...

Background Respiratory syncytial virus (RSV) is an important cause of severe lower respiratory tract illness in older adults. RSV and influenza are both typically seasonal diseases, with peaks during winter in temperate climates. Annual vaccination with high-dose or adjuvanted influenza vaccine formulations is recommended to prevent influenza illne...

Background A variant-adapted bivalent BNT162b2 mRNA vaccine (bivalent BNT162b2) comprising original SARS-CoV-2 and Omicron BA.4/BA.5 spike proteins is authorized by the US FDA from 6 months of age as a primary series or as booster doses. We studied whether bivalent BNT162b2 booster generates improved immune responses against Omicron BA.4/BA.5 and a...

Background A variant-adapted bivalent BNT162b2 vaccine (bivalent BNT162b2) comprised of original SARS-CoV-2 and Omicron BA.4/BA.5 spike proteins was developed to improve protection against SARS-CoV-2 variants. Bivalent BNT162b2 is authorized by the US FDA from 6 months (mo) old; for children 6 mo to < 5 years (y), it is authorized as a 3-dose prima...

Background RENOIR is a phase 3 randomized, double-blinded, placebo-controlled study evaluating Vaccine Efficacy (VE) to prevent lower respiratory tract illness (LRTI) in adults ≥ 60 years of age during 2 RSV seasons in Northern and Southern Hemisphere countries (NCT05035212). End of RSV Season 1 (EoS1) analysis demonstrated VE of 88.9% for RSV-asso...

Background Respiratory syncytial virus (RSV) is an important cause of lower respiratory tract illness (LRTI) in older adults. The search for an effective RSV vaccine was hindered by poor functional immunogenicity of early vaccine candidates that did not have F antigens stabilized in the prefusion state. RSVpreF, Pfizer’s bivalent stabilized prefusi...

Background The 20-valent pneumococcal conjugate vaccine (PCV20), developed to expand protection against pneumococcal disease, is approved for adults in several countries and for pediatric use in the United States. Tolerability and safety data from PCV20 pediatric studies are described. Methods Five randomized studies in infants (1 Phase 2; 4 Phase...

Background Respiratory Syncytial Virus (RSV)-related disease poses an economic burden due to a substantial amount of health care utilization (HCU). RENOIR is a phase 3 global, multicenter, randomized, double-blinded, placebo-controlled study evaluating vaccine efficacy (VE) in adults ≥60 years of age during two RSV seasons in Northern and Southern...

Background Respiratory syncytial virus (RSV) and influenza are both typically seasonal diseases, with winter peaks in temperate climates. Coadministration of an RSV vaccine and influenza vaccine could be a benefit, requiring 1 rather than 2 visits to a healthcare provider for individuals receiving both vaccines. Methods The primary immunogenicity...

Vaccination is a critical tool for preventing coronavirus disease 2019 (COVID-19) and influenza illnesses. Coadministration of the COVID-19 vaccine, BNT162b2, with seasonal inactivated influenza vaccine (SIIV) can provide substantial benefits, including streamlining vaccine delivery. In this phase 3 study, healthy 18- to 64-year-olds who had receiv...

Background: This phase 2 extension explored long-term antibody persistence of an investigational Clostridioides difficile vaccine and safety/tolerability and immunogenicity of dose 4 ∼12 months postdose 3. Methods: One year postdose 3, 300 healthy US 65-85-year-olds were randomized to Dose 4 of vaccine at previously-received antigen levels (100...

Streptococcus pneumoniae causes a considerable disease burden among children in China. Many isolates exhibit antimicrobial resistance but are often serotypes covered by the 13-valent pneumococcal conjugate vaccine (PCV13). Because the approved infant immunization schedule in China allows PCV13 vaccination only for those 6 weeks to 15 months of age,...

Use of pneumococcal conjugate vaccines (PCVs) has led to substantial reductions in the global burden of pediatric pneumococcal disease. Expansion of serotype coverage has been achieved by increasing PCV valency, but this may carry the potential risk of antibody interference. A complementary 7-valent PCV (cPCV7) including polysaccharide conjugates f...

Background: Natural history studies have correlated serotype-specific anti-capsular polysaccharide (CPS) IgG in newborns with a reduced risk of group B streptococcal disease. A hexavalent CPS-cross-reactive material 197 glycoconjugate vaccine (GBS6) is being developed as a maternal vaccine to prevent invasive group B streptococcus in young infants...

Background: Staphylococcus aureus is a global pathogen frequently responsible for healthcare-associated infections, including surgical site infections (SSIs). Current infection prevention and control approaches may be limited, with S aureus antibiotic resistance remaining problematic. Thus, a vaccine to prevent or reduce S aureus infection is crit...

Background: Older adults are at increased risk of adverse outcomes from pneumococcal disease and COVID-19. Vaccination is an established strategy for preventing both illnesses. This study evaluated the safety and immunogenicity of coadministration of the 20-valent pneumococcal conjugate vaccine (PCV20) and a booster (third dose) of BNT162b2 COVID-...

Background: Whether vaccination during pregnancy could reduce the burden of respiratory syncytial virus (RSV)-associated lower respiratory tract illness in newborns and infants is uncertain. Methods: In this phase 3, double-blind trial conducted in 18 countries, we randomly assigned, in a 1:1 ratio, pregnant women at 24 through 36 weeks' gestati...

Background: Respiratory syncytial virus (RSV) infection causes considerable illness in older adults. The efficacy and safety of an investigational bivalent RSV prefusion F protein-based (RSVpreF) vaccine in this population are unknown. Methods: In this ongoing, phase 3 trial, we randomly assigned, in a 1:1 ratio, adults (≥60 years of age) to rec...

In this ongoing study, substantially increased ancestral SARS-CoV-2 neutralizing responses were observed 1 month after a third 10-µg BNT162b2 dose given to 5–11-year-olds versus neutralizing responses post-dose 2. After dose 3, increased neutralizing responses against Omicron BA.1 and BA.4/BA.5 strains were also observed. The safety/tolerability pr...

Background: Safe and effective vaccines against coronavirus disease 2019 (Covid-19) are urgently needed in young children. Methods: We conducted a phase 1 dose-finding study and are conducting an ongoing phase 2-3 safety, immunogenicity, and efficacy trial of the BNT162b2 vaccine in healthy children 6 months to 11 years of age. We present result...

Introduction: Older adults are at increased risk of adverse outcomes from pneumococcal disease and influenza infections. Vaccination is an established strategy for preventing both illnesses. This study evaluated coadministration of 20-valent pneumococcal conjugate vaccine (PCV20) and an adjuvanted quadrivalent inactivated influenza vaccine (QIV)....

Background: The emergence of immune-escape variants of severe acute respiratory syndrome coronavirus 2 warrants the use of sequence-adapted vaccines to provide protection against coronavirus disease 2019. Methods: In an ongoing phase 3 trial, adults older than 55 years who had previously received three 30-μg doses of the BNT162b2 vaccine were ra...

What is this summary about? This is a summary of an article about part of a clinical study for the BNT162b2 COVID-19 vaccine, also called the Pfizer-BioNTech vaccine. The article was published in the New England Journal of Medicine in May 2021. This summary describes how the vaccine worked in participants 12- to 15-years old. The part of the study...

What is this summary about? This is a summary of an article about part of a clinical study for the BNT162b2 COVID-19 vaccine, also called the Pfizer-BioNTech vaccine. The article was published in the New England Journal of Medicine in September 2021. The part of the study described in the article began in July 2020 and is ongoing. This means that t...

The BNT162b2 bivalent BA.4/5 COVID-19 vaccine has been authorized to mitigate COVID-19 due to current Omicron and potentially future variants. New sublineages of SARS-CoV-2 Omicron continue to emerge and have acquired additional mutations, particularly in the spike protein, that may lead to improved viral fitness and immune evasion. The present stu...

The aim of this post hoc analysis was to describe the immunogenicity of the 20-valent pneumococcal conjugate vaccine (PCV20) in adults with chronic medical conditions or smoking that place them at increased risk of developing pneumococcal disease. Data from 2 phase 3, randomized, active-controlled, double-blind studies in pneumococcal vaccine-naive...

Background: Although human respiratory syncytial virus (RSV) is an important cause of illness and death in older adults, no RSV vaccine has been licensed. Methods: In a phase 2a study, we randomly assigned healthy adults (18 to 50 years of age), in a 1:1 ratio, to receive a single intramuscular injection of either bivalent prefusion F (RSVpreF)...

Background Respiratory syncytial virus (RSV) is an important cause of disease in older adults. We evaluated the safety and immunogenicity of a stabilized RSV prefusion F subunit (RSVpreF) vaccine candidate with/without adjuvant in adults 65 − 85 years. Methods Primary Cohort participants were equally randomized to 1 of 7 RSVpreF formulations: 60 µ...

Background: Respiratory syncytial virus (RSV), a major cause of illness and death in infants worldwide, could be prevented by vaccination during pregnancy. The efficacy, immunogenicity, and safety of a bivalent RSV prefusion F protein-based (RSVpreF) vaccine in pregnant women and their infants are uncertain. Methods: In a phase 2b trial, we rand...

Background: Active immunization with the BNT162b2 vaccine (Pfizer-BioNTech) has been a critical mitigation tool against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during the coronavirus disease 2019 (Covid-19) pandemic. In light of reports of waning protection occurring 6 months after the primary two-dose vaccine series...

Background: Pneumococcal conjugate vaccines (PCVs) have significantly reduced pneumococcal disease, but disease from non-PCV serotypes remains. Safety, tolerability, and immunogenicity of a 20-valent PCV (PCV20) were evaluated. Methods: This pivotal phase 3, randomized, double-blind study enrolled adults into 3 age groups (≥60, 50-59, 18-49 year...

Background: Respiratory syncytial virus (RSV) causes substantial morbidity and mortality in older adults and adults with comorbidities. An effective vaccine is needed. An investigational bivalent prefusion F vaccine (RSVpreF) was assessed in healthy adults. Methods: This phase 1/2 study randomized adults 18-85 years old to receive placebo or 60,...

Background: Protection against human respiratory syncytial virus (RSV) remains an unmet need potentially addressable by maternal immunization. This phase 1/2 study evaluated a bivalent prefusion F vaccine (RSVpreF) with antigens from RSV subgroups A and B. Methods: Adults 18-49 years old (N=618) were randomized to receive placebo or 60, 120, or...

We report interim safety and immunogenicity findings from an ongoing phase 1/2 study of BNT162b2 in healthy Japanese adults. Participants were randomized 3:1 to receive 2 intramuscular injections of 30 μg BNT162b2 or placebo 21 days apart. Overall, 160 individuals were randomized: 119 received BNT162b2, and 41 received placebo. Participants were st...

Introduction Individuals with an underlying malignancy have high risk of poor COVID-19 outcomes. In clinical trials, COVID-19 vaccines were safe and efficacious against infection, hospitalization, and death, but most trials excluded participants with cancer. We report results from participants with a history of past or active neoplasm (malignant or...

Background Safe, effective vaccines against coronavirus disease 2019 (Covid-19) are urgently needed in children younger than 12 years of age. Methods A phase 1, dose-finding study and an ongoing phase 2–3 randomized trial are being conducted to investigate the safety, immunogenicity, and efficacy of two doses of the BNT162b2 vaccine administered 2...

Introduction A 20-valent pneumococcal conjugate vaccine, PCV20, was developed to expand protection against vaccine-preventable pneumococcal disease. PCV20 contains the components of the 13-valent pneumococcal conjugate vaccine, PCV13, and includes capsular polysaccharide conjugates for 7 additional serotypes. Thus, PCV20 may cover those additional...

Background: Prevention of respiratory syncytial virus (RSV) disease in infants is an unmet vaccine need, and maternal immunization is a potential strategy to address this need. This study evaluated concomitant administration of RSV stabilized prefusion F subunit vaccine (RSVpreF) and tetanus toxoid, reduced diphtheria toxoid, and acellular pertuss...

Background: The development and widespread use of pneumococcal conjugate vaccines (PCVs) substantially reduced the global burden of pneumococcal disease. Expanding the serotypes covered by PCVs may further reduce disease burden. A 20-valent PCV (PCV20) has been developed to add coverage for 7 additional serotypes (8, 10A, 11A, 12F, 15B, 22F and 33...

At present, the dramatic rise in antimicrobial resistance (AMR) among important human bacterial pathogens is reaching a state of global crisis threatening a return to the pre-antibiotic era. AMR, already a significant burden on public health and economies, is anticipated to grow even more severe in the coming decades. Several licensed vaccines, tar...

BACKGROUND BNT162b2 is a lipid nanoparticle-formulated, nucleoside-modified RNA vaccine encoding a prefusion-stabilized, membrane-anchored severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) full-length spike protein. BNT162b2 is highly efficacious against coronavirus disease 2019 (Covid-19) and is currently approved, conditionally approve...

Background Two phase 1/phase 2 studies assessed 2 formulations of investigational bivalent Clostridioides (Clostridium) difficile vaccine (QS-21 adjuvanted toxoid and toxoid-alone) in healthy adults 50–85 years of age. Methods The QS-21 adjuvanted toxoid vaccine study randomized subjects 3:1 to 100 μg QS-21–containing C difficile vaccine or placeb...

Background: BNT162b2 is a lipid nanoparticle-formulated, nucleoside-modified RNA vaccine encoding a prefusion-stabilized, membrane-anchored SARS-CoV-2 full-length spike protein. BNT162b2 is highly efficacious against COVID-19 and is currently authorized for emergency use or conditional approval worldwide. At the time of authorization, data beyond 2...

Introduction Introduction of pneumococcal conjugate vaccines (PCVs), including the 13-valent PCV (PCV13), has considerably reduced pneumococcal disease burden. However, additional serotypes not in PCV13 continue to present a substantial disease burden. The 20-valent PCV (PCV20) was developed to expand protection against pneumococcal disease beyond...

Background Until very recently, vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had not been authorized for emergency use in persons younger than 16 years of age. Safe, effective vaccines are needed to protect this population, facilitate in-person learning and socialization, and contribute to herd immunity. Methods In...

Pneumococcal disease can be serious and debilitating in older adults. Pneumococcal conjugate vaccines (PCVs), such as the 13-valent PCV (PCV13), reduce pneumococcal disease rates caused by vaccine serotypes. Development of PCVs offering additional coverage against serotypes not contained in PCV13 can reduce disease burden further. The complementary...

Expanding serotype coverage of pneumococcal conjugate vaccines (PCVs) to target prevailing disease-causing serotypes could further reduce disease burden. To address this need, 2 different PCVs have been investigated: a 20-valent PCV (PCV20; includes the 13 serotypes in the 13-valent PCV [PCV13] plus 7 additional serotypes [8, 10A, 11A, 12F, 15B, 22...

A Correction to this paper has been published: https://doi.org/10.1038/s41586-020-03098-3.

The introduction of new classes of antibiotics, and the high use of antimicrobials in healthcare, agriculture, and the food industry, have all contributed to accelerate the development of antimicrobial resistance (AMR) in bacterial species and dissemination of antibiotic resistant bacterial strains worldwide. At present, the dramatic rise in AMR am...

Background A 20-valent pneumococcal conjugate vaccine (PCV20) is being developed to extend protection against pneumococcal disease beyond that of the 13-valent pneumococcal vaccine (PCV13). This is the first safety and immunogenicity study of PCV20 in healthy infants. Methods This randomized, double-blind study enrolled and randomized (1:1) health...

Background While widespread use of pneumococcal conjugate vaccines (PCVs) has reduced disease burden, expanding serotype coverage remains an unmet need in disease prevention. The 20-valent PCV (PCV20) contains capsular polysaccharide conjugates from serotypes included in the 13-valent PCV (PCV13; Prevnar 13®) as well as 7 additional serotypes. In a...

Background Two formulations of investigational bivalent Clostridioides (Clostridium) difficile vaccine (QS-21 adjuvanted toxoid and toxoid-alone) were assessed for safety and immunogenicity in randomized studies in healthy adults 50–85 years of age. Methods The Phase 1 study of QS-21 adjuvanted toxoid vaccine randomized subjects 3:1 to 100 μg QS-2...

Background Because of the number and variability of serotypes causing pneumococcal disease among different geographic regions, age groups, and environmental backgrounds, expanding serotype coverage with pneumococcal conjugate vaccines (PCVs) is a continued unmet need. Methods This phase 1, randomized, double-blind study included healthy Japanese a...

Background PCV20 contains the 13-valent pneumococcal conjugate vaccine (PCV13) components, and 7 additional conjugates (for serotypes 8, 10A, 11A, 12F, 15B, 22F, and 33F), extending pneumococcal serotype coverage. Key data from the pivotal Phase 3 evaluation of PCV20 in adults are presented. Methods Adults naïve to pneumococcal vaccination were en...

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (Covid-19) have afflicted tens of millions of people in a worldwide pandemic. Safe and effective vaccines are needed urgently. Methods Download a PDF of the Research Summary. In an ongoing multinational, placebo-controlled,...

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and the resulting disease, coronavirus disease 2019 (Covid-19), have spread to millions of persons worldwide. Multiple vaccine candidates are under development, but no vaccine is currently available. Interim safety and immunogenicity data about the vaccine candidate...

Background: Group B streptococcus (GBS) is a major cause of invasive disease in young infants. Infants born to women with sufficient pre-existing anti-GBS capsular IgG antibodies are at reduced risk of GBS disease, making maternal immunisation a potential strategy for prevention. We aimed to assess the safety and immunogenicity of a novel hexavale...

Background: Severe acute respiratory syndrome coronavirus 2 (SARS−CoV−2) infections and the resulting disease, coronavirus disease 2019 (COVID−19), have spread to millions of people globally. Multiple vaccine candidates are under development, but no vaccine is currently available. Methods: Healthy adults 18−55 and 65−85 years of age were randomized...