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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 described in the article is ongoing and expected to finish March 2023. This means that the final results may be different from the results included in this summary. What happened in this study? The part of the study described in this summary included participants 12- to 15-years old who had no serious health issues. The BNT162b2 vaccine had already been studied in participants 16 years of age or older. In this part of the study, the researchers wanted to find out: How effective and safe the vaccine was in participants 12- to 15-years old. What the immune response to the vaccine and the vaccine safety were like in 12- to 15-year-olds compared with 16- to 25-year-olds. How well the vaccine prevented SARS-CoV-2 infections in participants who received the vaccine compared to those who did not. This is also called efficacy of the BNT162b2 vaccine Half of the participants in this study received 2 injections of the BNT162b2 vaccine and half received 2 injections of a placebo in a muscle of the upper arm. The placebo looked like the BNT162b2 vaccine but did not have any active vaccine in it. What were the results? BNT162b2 had a favorable safety profile. The most common reactions were pain at the injection site, fatigue, and headache. None of the participants had serious reactions to the vaccine. The 12- to 15-year-old participants' immune system responses to the BNT162b2 vaccine were as good as or stronger than the 16- to 25-year-old participants' immune responses. The participants who received the BNT162b2 vaccine were less likely to get COVID-19 compared with the participants who got the placebo. Clinical Trial Registration: NCT04368728 ( ClinicalTrials.gov )

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 the final results may be different from the results included in this summary. What happened in this study? The participants in this study received 2 injections of either the BNT162b2 vaccine or a placebo, 21 days apart. The placebo looked like the BNT162b2 vaccine but had no active vaccine in it. None of the trial participants or study teams knew who received vaccine or placebo. What were the results? Most of the reactions to the injections were mild or moderate and lasted for a short period of time. The most common reactions were pain at the injection site, extreme tiredness (fatigue), and headache. These reactions usually happened in the first 7 days after receiving a vaccine dose. A small number of participants had severe reactions to the vaccine. Compared to participants who received the placebo, participants who received the BNT162b2 vaccine were much less likely to become ill if they were infected with the virus that causes COVID-19. The vaccine also had very good efficacy at preventing severe COVID-19. Participants in South Africa who received the BNT162b2 vaccine were less likely to become ill after infection with the beta variant of the virus compared to participants who received the placebo. The beta variant was very common in South Africa when the study was taking place. Clinical Trial Registration: NCT04368728 ( ClinicalTrials.gov )

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 aged 65–85 years. Methods Primary cohort participants were equally randomized to 1 of 7 RSVpreF formulations: 60 µg with either Al(OH)3 or CpG/Al(OH)3, 120 µg with either Al(OH)3 or CpG/Al(OH)3, 240 µg with either Al(OH)3 or CpG/Al(OH)3, 240 µg unadjuvanted, or placebo, administered concomitantly with high-dose seasonal inactivated influenza vaccine (SIIV). Participants in the month 0,2 cohort were randomized to RSVpreF 240 µg with CpG/Al(OH)3 or placebo, administered at months 0 and 2. Results All RSVpreF vaccine candidates elicited robust and persistent serum neutralizing responses when administered alone or with SIIV. There was no notable difference in neutralizing response between the formulations, including those containing CpG. In the month 0,2 cohort, there was no booster effect of dose 2. SIIV responses were similar or slightly lower with concomitant administration of RSVpreF. Most systemic and local reactions were mild and more frequent after RSVpreF than placebo. Conclusions RSVpreF formulations were well tolerated and elicited robust neutralizing responses in older adults; however, CpG/Al(OH)3 did not further enhance responses. Clinical Trials Registration. NCT03572062.

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.In a phase 2b trial, we randomly assigned pregnant women, at 24 through 36 weeks' gestation, to receive either 120 or 240 μg of RSVpreF vaccine (with or without aluminum hydroxide) or placebo. The trial included safety end points and immunogenicity end points that, in this interim analysis, included 50% titers of RSV A, B, and combined A/B neutralizing antibodies in maternal serum at delivery and in umbilical-cord blood, as well as maternal-to-infant transplacental transfer ratios.This planned interim analysis included 406 women and 403 infants; 327 women (80.5%) received RSVpreF vaccine. Most postvaccination reactions were mild to moderate; the incidence of local reactions was higher among women who received RSVpreF vaccine containing aluminum hydroxide than among those who received RSVpreF vaccine without aluminum hydroxide. The incidences of adverse events in the women and infants were similar in the vaccine and placebo groups; the type and frequency of these events were consistent with the background incidences among pregnant women and infants. The geometric mean ratios of 50% neutralizing titers between the infants of vaccine recipients and those of placebo recipients ranged from 9.7 to 11.7 among those with RSV A neutralizing antibodies and from 13.6 to 16.8 among those with RSV B neutralizing antibodies. Transplacental neutralizing antibody transfer ratios ranged from 1.41 to 2.10 and were higher with nonaluminum formulations than with aluminum formulations. Across the range of assessed gestational ages, infants of women who were immunized had similar titers in umbilical-cord blood and similar transplacental transfer ratios.RSVpreF vaccine elicited neutralizing antibody responses with efficient transplacental transfer and without evident safety concerns. (Funded by Pfizer; ClinicalTrials.gov number, NCT04032093.).

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 benign/unknown) and up to 6 months’ follow-up post-dose 2 from the placebo-controlled, observer-blinded trial of the 2-dose BNT162b2 mRNA COVID-19 vaccine. Patients and methods Between July 2020–January 2021, 46,429 participants aged ≥12 years were randomized at 152 sites in 6 countries. Healthy participants with pre-existing stable neoplasm could participate; those receiving immunosuppressive therapy were excluded. Data are reported for participants, aged ≥16 years for safety and ≥12 years for efficacy, who had any history of neoplasm at baseline (data cut-off: March 13, 2021). Adverse-event (AE) data are controlled for follow-up time before unblinding and reported as incidence rates (IRs) per 100 person-years follow-up. Results At baseline, 3813 participants had a history of neoplasm; most common malignancies were breast (n = 460), prostate (n = 362), and melanoma (n = 223). Four BNT162b2 and 71 placebo recipients developed COVID-19 from 7 days post-dose 2; vaccine efficacy was 94.4% (95% CI: 85.2, 98.5) after up to 6 months’ follow-up post-dose 2. This compares favorably with vaccine efficacy of 91.1% in the overall trial population after the same follow-up. AEs were reported at IRs of 95.4 (BNT162b2) and 48.3 (placebo) per 100 person-years. Most common AEs were reactogenicity events (injection-site pain, fatigue, pyrexia). Three BNT162b2 and 1 placebo recipients withdrew because of vaccine-related AEs. No vaccine-related deaths were reported. Conclusion In participants with past or active neoplasms, BNT162b2 vaccine has a similar efficacy and safety profile as in the overall trial population. These results can inform BNT162b2 use during the COVID-19 pandemic and future trials in participants with cancer. Clinical trial number: NCT04368728

Background Pneumococcal conjugate vaccines (PCVs) have significantly reduced pneumococcal disease, but disease from non-PCV serotypes remains. The 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, and 18–49 years) at US and Swedish sites. Participants were randomized to receive 1 PCV20 or 13-valent PCV (PCV13) dose. After 1 month, participants aged ≥60 years also received 1 dose of saline or 23-valent polysaccharide vaccine (PPSV23). Safety assessments included local reactions, systemic events, adverse events, serious adverse events, and newly diagnosed chronic medical conditions. Opsonophagocytic activity geometric mean titers 1 month after PCV20 were compared with 13 matched serotypes after PCV13 and 7 additional serotypes after PPSV23 in participants aged ≥60 years; noninferiority was declared if the lower bound of the 2-sided 95% confidence interval for the opsonophagocytic activity geometric mean titer ratio (ratio of PCV20/saline to PCV13/PPSV23 group) was >0.5. PCV20-elicited immune responses in younger participants were also bridged to those in 60–64-year-olds. Results The severity and frequency of prompted local reactions and systemic events were similar after PCV20 or PCV13; no safety concerns were identified. Primary immunogenicity objectives were met, with immune responses after PCV20 noninferior to 13 matched serotypes after PCV13 and to 6 additional PPSV23 serotypes in participants aged ≥60 years; serotype 8 missed the statistical noninferiority criterion. PCV20 induced robust responses to all 20 vaccine serotypes across age groups. Conclusions PCV20 was safe and well tolerated, with immunogenicity comparable to that of PCV13 or PPSV23. PCV20 is anticipated to expand protection against pneumococcal disease in adults. Clinical Trials Registration NCT03760146.

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, 120, or 240 µg RSVpreF (with or without aluminum hydroxide) alone or concomitantly with seasonal inactivated influenza vaccine (SIIV). Safety and immunogenicity were assessed. Results In older adults, reactogenicity events were predominantly mild or moderate among RSVpreF recipients; adverse events through 1 month postvaccination were similar across formulations. Coadministration with SIIV did not appear to affect safety among younger or older adults. All RSVpreF formulations with or without concomitant SIIV elicited robust RSV serum-neutralizing responses in adults aged 50–85 years 1 month postvaccination. Neutralizing titers 1 and 12 months postvaccination were 6.9–14.9 and 2.9–4.5 times, respectively, those before vaccination. SIIV immune responses trended lower when coadministered with RSVpreF. Conclusions RSVpreF formulations administered alone or with SIIV were well tolerated and highly immunogenic in older adults, supporting the potential for RSVpreF to protect older adults from RSV disease. Clinical Trials Registration NCT03529773.

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 240 µg RSVpreF with or without Al(OH)3. Safety and immunogenicity were evaluated. Results RSVpreF recipients more frequently reported local reactions and systemic events than placebo recipients; these were mostly mild or moderate. No vaccine-related serious adverse events occurred through 12 months postvaccination. All RSVpreF formulations induced 1-month postvaccination virus-neutralizing titers higher than those associated with protection of high-risk infants by palivizumab, the only prophylactic currently available for RSV. Geometric mean fold rises (GMFRs) across RSVpreF doses/formulations were 10.6–16.9 for RSV A and 10.3–19.8 for RSV B at 1 month postvaccination, greater than those historically elicited by postfusion F vaccines. GMFRs were 3.9–5.2 and 3.7–5.1, respectively, at 12 months postvaccination. Conclusions RSVpreF formulations were safe, well tolerated, and induced robust neutralizing responses in adults. These findings support development of RSVpreF, which is being evaluated in a pivotal phase 3 study for maternal immunization. Clinical Trials Registration NCT03529773.

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 approved, or authorized for emergency use worldwide. At the time of initial authorization, data beyond 2 months after vaccination were unavailable. Methods In an ongoing, placebo-controlled, observer-blinded, multinational, pivotal efficacy trial, we randomly assigned 44,165 participants 16 years of age or older and 2264 participants 12 to 15 years of age to receive two 30-μg doses, at 21 days apart, of BNT162b2 or placebo. The trial end points were vaccine efficacy against laboratory-confirmed Covid-19 and safety, which were both evaluated through 6 months after vaccination. Results BNT162b2 continued to be safe and have an acceptable adverse-event profile. Few participants had adverse events leading to withdrawal from the trial. Vaccine efficacy against Covid-19 was 91.3% (95% confidence interval [CI], 89.0 to 93.2) through 6 months of follow-up among the participants without evidence of previous SARS-CoV-2 infection who could be evaluated. There was a gradual decline in vaccine efficacy. Vaccine efficacy of 86 to 100% was seen across countries and in populations with diverse ages, sexes, race or ethnic groups, and risk factors for Covid-19 among participants without evidence of previous infection with SARS-CoV-2. Vaccine efficacy against severe disease was 96.7% (95% CI, 80.3 to 99.9). In South Africa, where the SARS-CoV-2 variant of concern B.1.351 (or beta) was predominant, a vaccine efficacy of 100% (95% CI, 53.5 to 100) was observed. Conclusions Through 6 months of follow-up and despite a gradual decline in vaccine efficacy, BNT162b2 had a favorable safety profile and was highly efficacious in preventing Covid-19. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04368728.)

Background Respiratory syncytial virus (RSV) is an important cause of disease in older adults and is associated with high morbidity and mortality, especially in those with high-risk conditions. Illness can vary from mild upper respiratory tract symptoms to more severe lower respiratory tract disease. After over 50 years of research, there is now hope for an RSV vaccine for any population, including older adults. An investigational bivalent RSV A and B, stabilized RSV prefusion F subunit vaccine (RSVpreF) was assessed successfully in a pivotal phase 3 efficacy study in older adults. (NCT05035212). Methods The primary efficacy objective of this Phase 3, global, multicenter, randomized, double-blinded, placebo-controlled study was to evaluate the prevention of RSV associated lower respiratory tract illness (LRTI-RSV) in up to 40,000 adults ≥60 years of age during the first winter season (September 2021-June 2022). Two primary endpoints were tested sequentially – LRTI-RSV with ≥2 and ≥3 symptoms. A pre-planned efficacy interim analysis (IA) was to be conducted by an external Data Monitoring Committee (DMC) upon accrual of at least 29 cases of LRTI-RSV with ≥2 symptoms. With efficacy demonstrated for cases with ≥2 symptoms and sufficient cases with ≥ 3 symptoms accrued, an efficacy analysis of cases with ≥ 3 symptoms was to be conducted. The ongoing study is collecting additional safety and descriptive efficacy data. Results At the time of the IA, approximately 34,000 participants received either RSVpreF 120 µg (60 µg each of RSVpreF from RSV A and RSV B) or placebo (1:1 randomization). Forty-four LRTI-RSV cases with ≥2 symptoms were accrued with 11 cases in the RSVpreF group and 33 cases in the placebo group corresponding to a VE of 66.7% (96.66% CI: 28.8%, 85.8%). Sixteen LRTI-RSV cases with ≥3 symptoms were accrued with 2 cases in the RSVpreF group and 14 cases in the placebo group corresponding to a VE of 85.7% (96.66% CI: 32.0%, 98.7%). The investigational vaccine was well-tolerated with no safety concerns. Conclusion Despite unpredictable RSV activity due to the COVID-19 pandemic, the primary objective of the study was met demonstrating that RSVpreF had a favorable safety profile and was highly efficacious in preventing LRTI-RSV with ≥2 symptoms and ≥3 symptoms in older adults 60 years and older. Disclosures Edward E. Walsh, MD, Janssen: Honoraria|Merck: Grant/Research Support|Pfizer: Grant/Research Support Fernando Polack, MD, I-trials: Ownership Interest|Pfizer: Grant/Research Support Agnieszka Zareba, MD PhD, Pfizer: employee of Pfizer Ann R. Falsey, MD, BioFire Diagnostics: Grant/Research Support|Janssen: Grant/Research Support|Merck Sharp & Dohme: Grant/Research Support|Novavax: Advisor/Consultant|Pfizer: Grant/Research Support Gonzalo Perez Marc, MD, I-trials: Board Member|I-trials: Ownership Interest|Pfizer: Grant/Research Support Qin Jiang, PhD, Pfizer: employee of Pfizer Kathy Schneider, PhD, Pfizer: employee of Pfizer David Cooper, PhD, Pfizer: employee of Pfizer Maria Maddalena Lino, PhD, Pfizer: employee of Pfizer Annaliesa S. Anderson, PhD, Pfizer: employee of Pfizer|Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Katherin U Jensen, PhD, Pfizer: employee of Pfizer Kena A. Swanson, Ph.D., Pfizer: employee of Pfizer Alejandra C. Gurtman, M.D., Pfizer: employee of Pfizer William C. Gruber, MD, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Beate Schmoele-Thoma, MD, Pfizer: employee of Pfizer.

Background Respiratory syncytial virus (RSV) is a major cause of infant morbidity and mortality worldwide and could be preventable by vaccination in pregnancy. Methods We conducted a randomized, placebo-controlled phase 2b trial evaluating safety, immunogenicity, and potential efficacy of a bivalent RSV prefusion F vaccine (RSVpreF) in pregnant women and their infants. Participants were randomized between 24- and 36-weeks’ gestation to receive 120 or 240 µg RSVpreF, with or without aluminum hydroxide, or placebo. Results This final analysis includes 579 women and 572 infants in 4 countries (Argentina, Chile, South Africa, and the US); 462 (79.8%) women received RSVpreF. Postvaccination reactions, most commonly injection site pain, fatigue, and myalgia, were generally mild-to-moderate. Adverse events (AEs) in the month following vaccination (maternal) or birth (infant) were mostly anticipated events in pregnancy and the neonatal period, respectively, and were similar between vaccine and placebo groups. No AEs were considered related to vaccination. For all RSVpreF groups, 50% neutralizing titers for both RSV-A and RSV-B rose sharply by 2 weeks after vaccination. At delivery occurring a mean of ∼8 weeks later, geometric mean titer (GMT) ratios for combined RSV-A/B between vaccine and placebo recipients’ infants were 10.9 to 13.6. Transplacental transfer ratios (all groups) were 1.39 to 1.83. Infant GMTs were higher in infants whose mothers had received RSVpreF versus placebo through 6 months of life; the estimated half-life of infant combined 50% RSV-A/B neutralizing titers was 41 days. Infants of women immunized across the range of assessed gestational ages had similar cord blood titers and transplacental transfer ratios. Observed efficacy (95% CI) against medically attended and severe medically attended infant RSV lower respiratory tract illness (LRTI) through 180 days in an exploratory analysis was 84.7% (21.5%, 97.6%) and 91.5% (-5.6%, 99.8%), respectively. Conclusion RSVpreF was well-tolerated in pregnant women, elicited robust neutralizing responses with efficient transplacental transfer, and has the potential to prevent infant RSV LRTI. Disclosures Eric A. F. Simões, MD, M.B., B.S., DCH, Abbvie: DSMB|Astra Zeneca: Grant/Research Support|Bill and Melinda Gates Foundation: Grant/Research Support|Bill and Melinda Gates Foundation: DSMB|GSK Inc.: DSMB|Johnson and Johnson: Grant/Research Support|Merck Inc: Advisor/Consultant|Merck Inc: Grant/Research Support|Nivavax: Grant/Research Support|Pfizer Inc: Advisor/Consultant|Pfizer Inc: Grant/Research Support|Regeneron: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant Shabir A. Madhi, MBBCh, FCPaeds, MMed, PhD, AstraZeneca: Funding to institution for conduct of study Kimberly J. Center, M.D., Pfizer: Employee|Pfizer: Stocks/Bonds Jose M. Novoa Pizarro, MD, AstraZeneca: Grant/Research Support|Medimmune: Grant/Research Support|MSD: Grant/Research Support|Pfizer: Grant/Research Support|Regeneron: Grant/Research Support Kena A. Swanson, Ph.D., Pfizer: employee of Pfizer David Radley, MS, Pfizer: Employee|Pfizer: Stocks/Bonds Stephanie B. McGrory, B.S.N., Pfizer: Employee|Pfizer: Stocks/Bonds Emily A. Gomme, Ph.D., Pfizer: Stocks/Bonds Daniel A. Scott, MD, Pfizer: Employee|Pfizer: Stocks/Bonds Kathrin U. Jansen, PhD, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds William C. Gruber, MD, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Alejandra C. Gurtman, M.D., Pfizer: employee of Pfizer.

Background Group B streptococcus (GBS) is a leading cause of invasive bacterial infections in young infants and pregnant women. Pfizer is developing a hexavalent GBS vaccine (GBS6) as a maternal vaccine to prevent invasive GBS disease due to the 6 most prevalent serotypes in young infants. We previously reported Phase 1 safety and immunogenicity data for GBS6. There is precedent for repeat doses of vaccines to augment or sustain circulating antibodies available for placental transfer with each pregnancy; thus, data to inform GBS6 booster strategies were required. Methods This was a Phase 2 open-label extension study to evaluate the safety and immunogenicity of a booster dose of GBS6 (20 μg capsular polysaccharide (CPS)/serotype/dose) with or without AlPO4, given ∼2 years after primary vaccination in 151 healthy nonpregnant adults. Sera taken before and 1-month postbooster were assessed for anti-CPS IgG using a direct Luminex immunoassay. Participants recorded solicited local and systemic events for 14 days after vaccination and unsolicited safety events through 6 months after vaccination. Immunogenicity time points from the Phase 1 study are referred to as primary dose. Results Immunogenicity results For all serotypes, serotype-specific IgG geometric mean concentrations (GMCs) remained elevated compared to baseline at the prebooster time point and were higher 1-month postbooster than 1 month post primary. The 1-month postbooster IgG GMCs were 10- to 59-fold higher than at the prebooster time point. There were similar responses between the 2 formulations. Safety and tolerability results The most frequently reported local reaction was mild to moderate pain at the injection site. Greater pain was associated with AlPO4 formulation. The most frequently reported systemic events were mild to moderate headache and fatigue. The frequency of adverse events was low. Figure 1Antibody Response Line Plot of IgG GMCs by Vaccine Group - All SerotypesFigure 2.Reverse Cumulative Distribution Curves (RCDCs) for IgG 1 Month After Primary and Booster Vaccination, by Vaccine Group – All SerotypesFigure 3.IgG Geometric Mean Fold Rises (GMFRs) at 1 Month Postbooster Vaccination Conclusion A booster dose of GBS6 given ∼2 years after a primary dose to healthy nonpregnant adults was safe and elicited robust immune responses that were also consistently higher than after primary dose. This study suggests that repeat vaccination with GBS6 may confer additional benefit in pregnant women in subsequent pregnancies. Disclosures Babalwa Jongihlati, MD, MBA, Pfizer: Stocks/Bonds Judith Absalon, MD, MPH, Pfizer: Stocks/Bonds Samantha Munson, MPH, MBA, Pfizer: Stocks/Bonds Yasmin Sanchez-Pearson, PhD, Pfizer: Stocks/Bonds Raphael Simon, PhD, Pfizer: Stocks/Bonds Natalie Silmon de Monerri, PhD, Pfizer: Stocks/Bonds David Radley, MS, Pfizer: Employee|Pfizer: Stocks/Bonds Emily A. Gomme, Ph.D., Pfizer: Stocks/Bonds Michelle Gaylord, PhD, Pfizer: Stocks/Bonds William C. Gruber, MD, Pfizer, Inc.: Salary|Pfizer, Inc.: Stocks/Bonds Kathrin U. Jansen, PhD, Pfizer: Stocks/Bonds Daniel A. Scott, MD, Pfizer: Employee|Pfizer: Stocks/Bonds Annaliesa S. Anderson, PhD, Pfizer: Stocks/Bonds.

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 study characterized neutralization activities against new Omicron sublineages BA.4.6, BA.2.75.2, BQ.1.1, and XBB.1 after a 4thdose (following three doses of BNT162b2) of either the original monovalent BNT162b2 or the bivalent BA.4/5 booster in individuals >55 years of age. For all participants, the 4thdose of monovalent BNT162b2 vaccine induced a 3.0×, 2.9×, 2.3×, 2.1×, 1.8×, and 1.5× geometric mean neutralizing titer fold rise (GMFR) against USA/WA1-2020 (a strain isolated in January 2020), BA.4/5, BA.4.6, BA.2.75.2, BQ.1.1, and XBB.1, respectively; the bivalent vaccine induced 5.8×, 13.0×, 11.1×, 6.7×, 8.7×, and 4.8× GMFRs. For individuals without SARS-CoV-2 infection history, BNT162b2 monovalent induced 4.4×, 3.0×, 2.5×, 2.0×, 1.5×, and 1.3× GMFRs, respectively; the bivalent vaccine induced 9.9×, 26.4×, 22.2×, 8.4×, 12.6×, and 4.7× GMFRs. These data suggest the bivalent BA.4/5 vaccine is more immunogenic than the original BNT162b2 monovalent vaccine against circulating Omicron sublineages, including BQ.1.1 that is becoming prevalent globally.

Supplemental Digital Content is available in the text., 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 33F) to those in the existing 13-valent PCV (PCV13). This phase 2 study evaluated the safety, tolerability and immunogenicity of PCV20 in healthy US infants. Methods: In this randomized, active-controlled, double-blind study, 460 infants were randomized 1:1 to receive a 4-dose series of either PCV20 or PCV13 at 2, 4, 6 and 12 months of age. Solicited local reactions and systemic events, adverse events (AEs) and serious AEs were recorded. Immunogenicity was assessed by measuring serotype-specific IgG concentrations and opsonophagocytic activity titers at 1 month after Dose 3, before Dose 4 and 1 month after Dose 4. Results: Of 460 infants, 82.8% completed the 1-month visit after Dose 4. Local reactions and systemic events were mostly mild to moderate in severity and similar between the PCV20 and PCV13 groups. Treatment-related AEs were uncommon, with no related serious AEs or deaths reported. IgG and opsonophagocytic activity responses elicited by PCV20 were robust and demonstrated a booster response after Dose 4. Conclusions: Administration of PCV20 in US infants was well tolerated, with a safety profile similar to PCV13, and induced robust serotype-specific immune responses. These findings support continued development of PCV20 in the pediatric population.

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 placebo administered in a shortened-month (Months 0, 1, 3) or day (Days 1, 8, 30) regimen. The toxoid-alone vaccine study randomized subjects 3:3:1 to receive 100 or 200 μg unadjuvanted C difficile vaccine formulation or placebo in Stages 1 and 2 (sentinel cohorts of different age groups), and 3:1 to receive the selected dose of unadjuvanted C difficile vaccine formulation or placebo in Stage 3 (Days 1, 8, 30). Safety was the primary outcome for both studies. Immunogenicity was determined by measuring serum toxin A– and B–specific neutralizing antibodies. Results In the day regimen, 10 reports across both studies of grade 3 injection site redness postdose 2 triggered predefined stopping rules. Local reactions in both studies were more common among vaccine versus placebo recipients. Injection site pain predominated and was generally mild in severity. Systemic events were infrequent and generally mild-to-moderate in severity. Adverse events were reported by 50.0%–75.0% and 16.7%–50.0% of subjects in the QS-21 and toxoid-alone studies, respectively. Immune responses peaked around Day 37 (shortened-month regimen) or between Day 15 and Month 2 (day regimen) and remained above baseline throughout follow-up. Conclusions Both formulations demonstrated robust immunogenicity. Both studies stopped early due to grade 3 injection site redness postdose 2 of the day regimen; neither formulation progressed to later stage development. Instead, an aluminum hydroxide-containing formulation of the vaccine candidate administered at 0, 1, and 6 months, which was safe and immunogenic in phase 1 and 2 studies, advanced to phase 3 studies.

Although human respiratory syncytial virus (RSV) is an important cause of illness and death in older adults, no RSV vaccine has been licensed.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) vaccine or placebo. Approximately 28 days after injection, participants were inoculated intranasally with the RSV A Memphis 37b challenge virus and observed for 12 days. The per-protocol prespecified primary end points were the following: reverse-transcriptase-quantitative polymerase-chain-reaction (RT-qPCR)-confirmed detectable RSV infection on at least 2 consecutive days with at least one clinical symptom of any grade from two categories or at least one grade 2 symptom from any category, the total symptom score from day 1 to discharge, and the area under the curve (AUC) for the RSV viral load in nasal-wash samples measured by means of RT-qPCR from day 2 after challenge to discharge. In addition, we assessed immunogenicity and safety.After participants were inoculated with the challenge virus, vaccine efficacy of 86.7% (95% CI, 53.8 to 96.5) was observed for symptomatic RSV infection confirmed by any detectable viral RNA on at least 2 consecutive days. The median AUC for the RSV viral load (hours × logRSVpreF vaccine was effective against symptomatic RSV infection and viral shedding. No evident safety concerns were identified. These findings provide support for further evaluation of RSVpreF vaccine in a phase 3 efficacy study. (Funded by Pfizer; EudraCT number, 2020-003887-21; ClinicalTrials.gov number, NCT04785612.).

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 7-valent PCV (cPCV7) contains seven non-PCV13 serotypes (8, 10A, 11A, 12F, 15B, 22F, 33F) and can expand coverage by supplementing direct or indirect protection from existing PCVs. This phase 1/2, randomized, active-controlled, observer-blinded study evaluated cPCV7 safety and immunogenicity in healthy adults 50–85 years of age. Stage 1 randomized 66 healthy adults (50–64 years) naive to pneumococcal vaccines to receive cPCV7 or licensed tetanus, diphtheria, and acellular pertussis vaccine; Stage 2 randomized 445 healthy adults (65–85 years) previously vaccinated with PCV13 to receive cPCV7 or 23-valent polysaccharide vaccine. Local reactions and systemic events up to 14 days and adverse events (AEs) through 1 month after vaccination were assessed. Immunogenicity was evaluated by serotype-specific opsonophagocytic activity (OPA) assays before and 1 month after vaccination (and after 12 months in Stage 2). Rates of local reactions, systemic events, and AEs were generally similar after receipt of cPCV7 or control. Robust OPA responses were observed for all seven serotypes 1 month after cPCV7; titers declined yet remained above baseline 12 months after vaccination. Overall, this study found that in adults ≥50 years of age, cPCV7 was safe, well tolerated, and elicited functional immune responses to vaccine serotypes. ClinicalTrials.gov: NCT03313050

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, 22F, 33F]) and a complementary 7-valent PCV (cPCV7; contains only the 7 additional serotypes). This phase 1b, randomized, controlled, double-blind study evaluated PCV20 and cPCV7 safety and immunogenicity in healthy Japanese adults 18–49 years of age residing in the United States for ≤5 years. Participants (n = 104) were randomized equally to receive a single dose of PCV20, cPCV7, or PCV13. Immunogenicity was assessed at baseline and 1 month after vaccination using serotype-specific opsonophagocytic activity (OPA) titers and serotype-specific immunoglobulin G (IgG) concentrations. Prompted local reactions and systemic events; adverse events (AEs); and serious AEs and newly diagnosed chronic disease were assessed 14 days, through 1 month, and upto 6 months following vaccination, respectively. OPA immune responses were robust for all 20 serotypes in the PCV20 group and for the 7 serotypes in the cPCV7 group 1 month after vaccination. IgG immune response showed similar trends. Injection site pain and muscle pain were the most common local reaction and systemic event; the majority were mild or moderate in severity. Few AEs and no severe AEs, serious AEs, or safety-related withdrawals were reported. Taken together, administration of PCV20 or cPCV7 in Japanese adults was well tolerated and induced robust serotype-specific functional immune responses. NCT03642847.

Summary 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 hexavalent (serotypes Ia, Ib, II, III, IV, and V) GBS conjugate vaccine (GBS6). Methods This phase 1/2, placebo-controlled, observer-blinded, dose-escalation trial, was done at four clinical research centres in the USA (Kentucky, Georgia, and two sites in Utah). Healthy, non-pregnant adults aged 18–49 years were randomly assigned using an interactive, web-based response technology system. Within each dose group (low, medium, or high), participants in sentinel cohorts were randomly assigned 2:2:1 and expanded cohort participants were randomly assigned 4:4:1 to receive GBS6 with aluminium phosphate (AlPO4), GBS6 without AlPO4, or placebo (saline control). One 0·5 mL dose of either saline placebo or 5 μg capsular polysaccharide per serotype in the low-dose group, 10 μg capsular polysaccharide per serotype in the medium-dose group, or 20 μg capsular polysaccharide per serotype in the high-dose group was administered by intramuscular injection into the deltoid muscle on day 1. The primary outcome was safety up to 6 months after vaccination, including the proportion of sentinel cohort participants with clinical laboratory abnormalities at 1 week, the proportion of all participants reporting solicited local reactions, systemic events, or use of antipyretic or pain medication within 14 days, adverse events up to 1 month, and medically attended or serious adverse events up to 6 months. The secondary outcome was GBS immunogenicity (serotype-specific IgG geometric mean concentrations at 1 month). This study is registered with ClinicalTrials.gov , NCT03170609 . Findings Between June 5, 2017, and June 25, 2018, 365 participants were randomly assigned and 364 (52 in each dose group) were vaccinated and included in the safety analysis. Unsolicited adverse events were reported by 15 (29%) participants in the 5 μg with AlPO4 group, 13 (25%) in the 5 μg without AlPO4 group, 22 (42%) in the 10 μg with AlPO4 group, 12 (23%) in the 10 μg without AlPO4 group, 25 (48%) in the 20 μg with AlPO4 group, 21 (40%) in the 20 μg without AlPO4 group, and 20 (38%) in the placebo group. The most common unsolicited adverse events were in the system organ class of infections and infestations in any dose or formulation of GBS6 (ranging from six [12%] in the 10 μg without AlPO4 group to 15 [29%] in the 20 μg with AlPO4 group and placebo group). Three participants reported at least one serious adverse event during the study, one each in the 5 μg GBS6 with AlPO4 group (diabetic ketoacidosis, two events; resolved), 10 μg GBS6 with AlPO4 group (died by suicide), and 20 μg GBS6 with AlPO4 group (metrorrhagia; resolved). None of these serious adverse events were considered related to the vaccine. 11 of the 365 participants were excluded from the evaluable immunogenicity population, including one participant who did not receive the vaccine, and ten who at 1 month after vaccination were withdrawn for various reasons. GBS serotype-specific IgG geometric mean concentrations increased by 1 week after vaccination for all GBS6 groups, peaked at 2 weeks, stabilised by 1 month, and declined gradually but remained higher than placebo at 6 months. Interpretation GBS6 was well tolerated in healthy adults and elicited robust immune responses for all dose levels and formulations that persisted 6 months after vaccination. This study supports further evaluation of GBS6 in pregnant women. Funding Pfizer.

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, data are needed on the safety and efficacy of offering a third (booster) dose in persons 16 years of age or older.In this ongoing, placebo-controlled, randomized, phase 3 trial, we assigned participants who had received two 30-μg doses of the BNT162b2 vaccine at least 6 months earlier to be injected with a third dose of the BNT162b2 vaccine or with placebo. We assessed vaccine safety and efficacy against Covid-19 starting 7 days after the third dose.A total of 5081 participants received a third BNT162b2 dose and 5044 received placebo. The median interval between dose 2 and dose 3 was 10.8 months in the vaccine group and 10.7 months in the placebo group; the median follow-up was 2.5 months. Local and systemic reactogenicity events from the third dose were generally of low grade. No new safety signals were identified, and no cases of myocarditis or pericarditis were reported. Among the participants without evidence of previous SARS-CoV-2 infection who could be evaluated, Covid-19 with onset at least 7 days after dose 3 was observed in 6 participants in the vaccine group and in 123 participants in the placebo group, which corresponded to a relative vaccine efficacy of 95.3% (95% confidence interval, 89.5 to 98.3).A third dose of the BNT162b2 vaccine administered a median of 10.8 months after the second dose provided 95.3% efficacy against Covid-19 as compared with two doses of the BNT162b2 vaccine during a median follow-up of 2.5 months. (Funded by BioNTech and Pfizer; C4591031 ClinicalTrials.gov number, NCT04955626.).

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)1, a pandemic. With rapidly accumulating numbers of cases and deaths reported globally2, 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. In a dose-escalation study of the COVID-19 RNA vaccine BNT162b1 in 45 healthy adults, RBD-binding IgG concentrations and SARS-CoV-2 neutralizing titres in sera increased with dose level and after a second vaccine dose.

Background 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. Methods 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. Results 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. Conclusions 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. Clinical Trials Registration NCT03313037., A 20-valent pneumococcal conjugate vaccine (PCV20) is being developed to expand serotype coverage beyond the 13-valent PCV (PCV13). In older adults, PCV20 exhibited safety and tolerability consistent with PCV13. PCV20 elicited robust immune responses to all 20 vaccine serotypes.

Background In 2010, the 13-valent pneumococcal conjugate vaccine (PCV13) replaced 7-valent PCV (PCV7) for protection against invasive pneumococcal disease (IPD). This study used laboratory surveillance data to examine the effect of PCV13 on IPD before and after PCV13 introduction among children aged 6 weeks to, In this prospective, laboratory-based surveillance study of Kaiser Permanente Northern California members, we examined annual invasive pneumococcal disease (IPD) incidence before and after 13-valent pneumococcal conjugate vaccine (PCV13) introduction. In children aged 6 weeks to

Background Pneumococcal conjugate vaccines (PCVs) elicit lower immune response against serotypes carried before or at the time of vaccination (hyporesponsiveness) in infants. The limited studies conducted to date did not permit comprehensive insights regarding this phenomenon. This study, the largest ever conducted with both carriage and serologic endpoints, attempted to add insight on serotype-specific hyporesponsiveness in relation to the number of PCV doses administered before carriage acquisition. Methods In a double-blind randomized clinical trial (n = 1754 infants), 7-valent or 13-valent PCV was administered at ages 2, 4, 6, and 12 months. New acquisition was defined based on nasopharyngeal swabs at ages 2, 4, 6, 7, and 12 months. Serotype-specific immunoglobulin G levels were obtained 1 month after the infant series and 1 month after the toddler dose. Results A lower immune response after the infant series and the toddler dose was consistently observed for carriers of serotypes 6A, 6B, 18C, and 19F at predefined time points, with a similar trend observed in carriers of serotype 23F. In contrast, carriage of serotypes 9V, 14, and 19A did not generally affect immune responses. For some but not all serotypes, hyporesponsiveness was decreased with an increased number of vaccine doses received before acquisition. A complex interrelationship between carriage and immune response was observed between cross-reacting serotypes. Conclusions Carrier-induced hyporesponsiveness to PCVs is common, differs among serotypes, and depends on timing of carriage acquisition and prior number of administered PCV doses. Clinical Trials Registration NCT00508742., Serotype-specific hyporesponsiveness of serological response to pneumococcal conjugate vaccines following acquisition of commonly carried pneumococcal serotypes in infants is complex and dependent on serotype and number of previous vaccine doses. This analysis showed no hyporesponsiveness following carriage of cross-reacting serotypes.

Objectives Assess Staphylococcus aureus (S. aureus) colonization in healthy Australian adults receiving an investigational S. aureus 3-antigen vaccine (SA3Ag). Methods In this phase 1, double-blind, sponsor-unblinded study, participants were randomized to receive a single dose (1 of 3 dose levels) of SA3Ag or placebo and a booster dose or placebo at 6 months. S. aureus isolates from nasal, perineal, and oropharyngeal swabs before and through 12 months post-vaccination were identified. Results Baseline S. aureus colonization prevalence was 30.6% (any site), with nasal carriage (27.0%) more common than oropharyngeal/perineal (3.2% each). Following initial vaccination (low-dose: 102; mid-dose: 101; high-dose: 101; placebo: 102) and booster (low-dose: 45; mid-dose: 44; high-dose: 27; placebo: 181), placebo and SA3Ag groups showed similar S. aureus carriage through 12 months. Most colonized participants (74.0%) were colonized by single spa types. Placebo and SA3Ag groups had similar persistence of colonization, with 19.6–30.7% due to single spa types. Acquisition was observed in mid- and high-dose recipients (∼20%) and low-dose and placebo recipients (∼12%). Vaccination resulted in substantial increases in antibodies to all 3 antigens, irrespective of carriage status. Conclusions Based on descriptive analyses of this small study, SA3Ag vaccination did not impact S. aureus acquisition or carriage. Carriage status did not impact antibody responses to SA3Ag.

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 21 days apart in children 6 months to 11 years of age. We present results for 5-to-11-year-old children. In the phase 2-3 trial, participants were randomly assigned in a 2:1 ratio to receive two doses of either the BNT162b2 vaccine at the dose level identified during the open-label phase 1 study or placebo. Immune responses 1 month after the second dose of BNT162b2 were immunologically bridged to those in 16-to-25-year-olds from the pivotal trial of two 30-μg doses of BNT162b2. Vaccine efficacy against Covid-19 at 7 days or more after the second dose was assessed. Results During the phase 1 study, a total of 48 children 5 to 11 years of age received 10 μg, 20 μg, or 30 μg of the BNT162b2 vaccine (16 children at each dose level). On the basis of reactogenicity and immunogenicity, a dose level of 10 μg was selected for further study. In the phase 2-3 trial, a total of 2268 children were randomly assigned to receive the BNT162b2 vaccine (1517 children) or placebo (751 children). At data cutoff, the median follow-up was 2.3 months. In the 5-to-11-year-olds, as in other age groups, the BNT162b2 vaccine had a favorable safety profile. No vaccine-related serious adverse events were noted. One month after the second dose, the geometric mean ratio of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing titers in 5-to-11-year-olds to those in 16-to-25-year-olds was 1.04 (95% confidence interval [CI], 0.93 to 1.18), a ratio meeting the prespecified immunogenicity success criterion (lower bound of two-sided 95% CI, >0.67; geometric mean ratio point estimate, ≥0.8). Covid-19 with onset 7 days or more after the second dose was reported in three recipients of the BNT162b2 vaccine and in 16 placebo recipients (vaccine efficacy, 90.7%; 95% CI, 67.7 to 98.3). Conclusions A Covid-19 vaccination regimen consisting of two 10-μg doses of BNT162b2 administered 21 days apart was found to be safe, immunogenic, and efficacious in children 5 to 11 years of age. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04816643.).

Vaccine Clinical Development is an integrated part of the overall process of vaccine development, which involves clinical trials in which study participants are usually prospectively and randomly allocated to receive the vaccine candidate or a control vaccine. Participants are then actively monitored to generate information on safety, and often immune responses and/or cases of the target disease. Clinical development starts with small phase 1 studies in tens or hundreds of volunteers. In phase 2, volunteers in the target population are studied for safety and evidence of a desired effect, often an immune response. In phase 3, pivotal studies will generally examine prevention of the target disease with at least 3000 participants receiving the vaccine candidate. The key outputs are reports for regulatory agencies, policy makers and health care workers to support marketing approval and appropriate ways to use the vaccine. Clinical trial designs and results are made public through registries and peer-reviewed publications.

Immune Response to a Third Dose of BNT162b2 A third dose of the BNT162b2 vaccine was administered to 23 volunteers 8 to 9 months after the second dose, and the immune response was assessed. Local r...