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Background The aim of this study was to investigate safety and immunogenicity of vaccine formulations against respiratory syncytial virus (RSV) containing the stabilized prefusion conformation of RSV fusion protein (RSVPreF3). Methods This phase 1/2, randomized controlled, observer-blind study enrolled 48 young adults (YAs; aged 18–40 years) and 1005 older adults (OAs; aged 60–80 years) between January and August 2019. Participants were randomized into equally sized groups to receive 2 doses of unadjuvanted (YAs and OAs) or AS01-adjuvanted (OAs) vaccine or placebo 2 months apart. Vaccine safety and immunogenicity were assessed until 1 month (YAs) or 12 months (OAs) after second vaccination. Results The RSVPreF3 vaccines boosted humoral (RSVPreF3-specific immunoglobulin G [IgG] and RSV-A neutralizing antibody) responses, which increased in an antigen concentration-dependent manner and were highest after dose 1. Compared to prevaccination, the geometric mean frequencies of polyfunctional CD4+ T cells increased after each dose and were significantly higher in adjuvanted than unadjuvanted vaccinees. Postvaccination immune responses persisted until end of follow-up. Solicited adverse events were mostly mild to moderate and transient. Despite a higher observed reactogenicity of AS01-containing vaccines, no safety concerns were identified for any assessed formulation. Conclusions Based on safety and immunogenicity profiles, the AS01E-adjuvanted vaccine containing 120 μg of RSVPreF3 was selected for further clinical development. Clinical Trials Registration NCT03814590.

Background RSV-associated acute respiratory infections (ARI), particularly lower respiratory tract diseases (LRTD), present a significant disease burden in older adults. Currently, there are no approved vaccines against RSV. We present results from an ongoing study designed to demonstrate the vaccine efficacy (VE) of the AS01E-adjuvanted RSVPreF3 OA in adults ≥ 60 YOA. Methods This ongoing, phase 3, observer-blind, placebo-controlled, multi-country study (NCT04886596) enrolled adults ≥ 60 YOA from the northern and southern hemispheres. Participants were randomized (1:1) to receive a single dose of RSVPreF3 OA or placebo before the RSV season. The primary objective was to demonstrate VE of a single dose of RSVPreF3 OA in preventing RSV-confirmed LRTD during one RSV season (criterion: lower limit of VE confidence interval [CI] > 20%). VE is reported also against severe RSV-confirmed LRTD, RSV-confirmed ARI, RSV-confirmed LRTD and RSV-confirmed ARI by RSV subtype (RSV-A and RSV-B), and RSV-confirmed LRTD by age, baseline comorbidity and frailty status. RSV-A/B was confirmed by quantitative RT-PCR. Results A total of 26,664 participants were enrolled, of whom 24,966 (RSVPreF3 OA: 12,467; placebo: 12,499) were included in the exposed set and 24,960 (RSVPreF3 OA: 12,466; placebo: 12,494) in the efficacy analysis. The mean age was 69.5 (±6.5) years and 51.7% were women. Over a median follow-up of 6.7 months (maximum 10.1 months), 47 RSV-confirmed LRTD episodes were reported (RSVPreF3 OA: 7; placebo: 40), resulting in a VE of 82.6% (96.95% CI: 57.9–94.1), thus the primary objective was met. Consistently high VE across the clinical spectrum of RSV disease, from RSV-confirmed ARI (71.7% [95% CI: 56.2–82.3]) to severe RSV-confirmed LRTD (94.1% [95% CI: 62.4–99.9]) was observed. High VE was seen in different age groups and regardless of RSV subtype, baseline comorbidity or pre-frail status (Figure 1). Cumulative incidence curves for RSV-confirmed LRTD and RSV-confirmed ARI showed persistent efficacy throughout the follow-up (Figure 2). Conclusion A single RSVPreF3 OA dose is highly efficacious against RSV-confirmed LRTD and RSV-confirmed ARI in adults ≥ 60 YOA, regardless of RSV disease severity, RSV subtype, baseline comorbidity and pre-frail status. Funding: GlaxoSmithKline Biologicals SA. Abstract and information is also available at the following link : Efficacy results for GSK's older adult RSV vaccine (investis.com). Disclosures Michael G. Ison, MD MS, GlaxoSmithKline: Advisor/Consultant|GlaxoSmithKline: Grant/Research Support Alberto Papi, MD, CHIESI, ASTRAZENECA, GSK, BI, MENARINI, NOVARTIS, ZAMBON, MUNDIPHARMA, SANOFI, AVILLION: Honoraria|CHIESI, ASTRAZENECA, GSK, NOVARTIS, SANOFI, IQVIA, AVILLION, ELPEN PHARMACEUTICALS: Advisor/Consultant|CHIESI, ASTRAZENECA, GSK, NOVARTIS, SANOFI, IQVIA, AVILLION, ELPEN PHARMACEUTICALS: Board Member|CHIESI, ASTRAZENECA, GSK, SANOFI: Grant/Research Support Joanne M. Langley, MD, GSK, Merck, Medicago, Sanofi, VBI, VIDO, Entos, Pfizer: Grant/Research Support Isabel Leroux-Roels, PhD MD, Curevac: payment to my institution for the conduct of clinical trials|GSK: payment to my institution for the conduct of clinical trials|ICON Genetics: payment to my institution for the conduct of clinical trials|Janssen Vaccines (J&J): Board Member|Janssen Vaccines (J&J): payment to my institution for the conduct of clinical trials|Osivax: payment to my institution for the conduct of clinical trials Federico Martinon-Torres, MD, PhD, Assoc. Prof, GlaxoSmithKline, Pfizer, Sanofi, Merck, Moderna, Astra Zeneca, Biofabri, Janssen, Novavax: Advisor/Consultant|GlaxoSmithKline, Pfizer, Sanofi, Merck, Moderna, Astra Zeneca, Biofabri, Janssen, Novavax: Grant/Research Support|GlaxoSmithKline, Pfizer, Sanofi, Merck, Moderna, Astra Zeneca, Biofabri, Janssen, Novavax: Honoraria|GlaxoSmithKline, Pfizer, Sanofi, Merck, Moderna, Astra Zeneca, Biofabri, Janssen, Novavax: Clínical trials fees paid to my institution Tino F. Schwarz, Prof. Dr. MD, GlaxoSmithKline: Advisor/Consultant Richard N. Van Zyl-Smit, PhD MD, MSD, Pfizer, GSK, Astra Zeneca, Roche, Novartis, Boehringer Ingelheim, Cipla, J&J, Glenmark: Advisor/Consultant|MSD, Pfizer, GSK, Astra Zeneca, Roche, Novartis, Boehringer Ingelheim, Cipla, J&J, Glenmark: Honoraria Nancy Dezutter, PhD, PharmD, GlaxoSmithKline: GSK employee|GlaxoSmithKline: Stocks/Bonds Nathalie De Schrevel, PhD, GlaxoSmithKline: GSK employee Laurence Fissette, Master in Statistics, GlaxoSmithKline: GSK employee|GlaxoSmithKline: Stocks/Bonds Marie-Pierre David, Master in Statistics, GlaxoSmithKline: GSK employee|GlaxoSmithKline: Stocks/Bonds Marie Van Der Wielen, MD, GlaxoSmithKline: GSK employee|GlaxoSmithKline: Stocks/Bonds Lusine Kostanyan, MD, GlaxoSmithKline: GSK employee|GlaxoSmithKline: Stocks/Bonds Veronica Hulstrøm, PhD MD, GlaxoSmithKline: GSK employee.

The aim was to investigate safety and immunogenicity of vaccine formulations against respiratory syncytial virus (RSV) containing the stabilized prefusion conformation of RSV fusion protein (RSVPreF3).This phase I/II, randomized, controlled, observer-blind study enrolled 48 young adults (YA; 18-40 years) and 1005 older adults (OA; 60-80 years) between January and August 2019. Participants were randomized into equally sized groups to receive two doses of unadjuvanted (YA and OA) or AS01-adjuvanted (OA) vaccine or placebo two months apart. Vaccine safety and immunogenicity were assessed until one (YA) or 12 months (OA) after second vaccination.The RSVPreF3 vaccines boosted humoral (RSVPreF3-specific IgG and RSV-A neutralizing antibody) responses, which increased in an antigen-concentration-dependent manner and were highest post-dose one. Compared to pre-vaccination, the geometric mean frequencies of polyfunctional CD4+ T-cells increased after each dose and were significantly higher in adjuvanted than unadjuvanted vaccinees. Post-vaccination immune responses persisted until end of follow-up. Solicited adverse events (AEs) were mostly mild-to-moderate and transient. Despite a higher observed reactogenicity of AS01-containing vaccines, no safety concerns were identified for any assessed formulation.Based on safety and immunogenicity profiles, the AS01E-adjuvanted vaccine containing 120 μg of RSVPreF3 was selected for further clinical development.ClinicalTrials.gov NCT03814590; URL: https://clinicaltrials.gov/ct2/show/NCT03814590.

Background Respiratory syncytial virus (RSV) disease is a major cause of infant morbidity and mortality. This Phase I, randomized, observer-blind, placebo- and active-controlled study evaluated an investigational vaccine against RSV (ChAd155-RSV) using the viral vector chimpanzee-adenovirus-155, encoding RSV fusion (F), nucleocapsid, and transcription antitermination proteins. Methods Healthy 18–45-year-old adults received ChAd155-RSV, a placebo, or an active control (Bexsero) at Days (D) 0 and 30. An escalation from a low dose (5 × 109 viral particles) to a high dose (5 × 1010 viral particles) occurred after the first 16 participants. Endpoints were solicited/unsolicited and serious adverse events (SAEs), biochemical/hematological parameters, cell-mediated immunogenicity by enzyme-linked immunospot, functional neutralizing antibodies, anti RSV-F immunoglobin (Ig) G, and ChAd155 neutralizing antibodies. Results There were 7 participants who received the ChAd155-RSV low dose, 31 who received the ChAd155-RSV high dose, 19 who received the placebo, and 15 who received the active control. No dose-related toxicity or attributable SAEs at the 1-year follow-up were observed. The RSV-A neutralizing antibodies geometric mean titer ratios (post/pre-immunization) following a high dose were 2.6 (D30) and 2.3 (D60). The ratio of the fold-rise (D0 to D30) in anti-F IgG over the fold-rise in RSV-A–neutralizing antibodies was 1.01. At D7 after the high dose of the study vaccine, the median frequencies of circulating B-cells secreting anti-F antibodies were 133.3/106 (IgG) and 16.7/106 (IgA) in peripheral blood mononuclear cells (PBMCs). The median frequency of RSV-F–specific interferon γ–secreting T-cells after a ChAd155-RSV high dose was 108.3/106 PBMCs at D30, with no increase after the second dose. Conclusions In adults previously naturally exposed to RSV, ChAd155-RSV generated increases in specific humoral and cellular immune responses without raising significant safety concerns. Clinical Trials Registration NCT02491463., We investigated the safety and immunogenicity of a novel chimpanzee-adenovirus-155 vaccine against respiratory syncytial virus (RSV; ChAd155-RSV). In healthy adults with previous natural RSV exposure, ChAd155-RSV generated antigen-specific humoral and cellular immune responses without raising significant safety concerns.

A recombinant respiratory syncytial virus (RSV) fusion glycoprotein candidate vaccine (RSV-PreF) manufactured in Chinese hamster ovary cells was developed for immunization of pregnant women, to protect newborns against RSV disease through trans-placental antibody transfer. Traces of a host-cell protein, hamster neogenin (haNEO1), were identified in purified RSV-PreF antigen material. Given the high amino-acid sequence homology between haNEO1 and human neogenin (huNEO1), there was a risk that potential vaccine-induced anti-neogenin immunity could affect huNEO1 function in mother or fetus. Anti-huNEO1 IgGs were measured by enzyme-linked immunosorbent assay in sera from rabbits and trial participants (Phase 1 and 2 trials enrolling 128 men and 500 non-pregnant women, respectively; NCT01905215/NCT02360475) collected after immunization with RSV-PreF formulations containing different antigen doses with/without aluminum-hydroxide adjuvant. In rabbits, four injections administered at 14-day intervals induced huNEO1-specific IgG responses in an antigen-dose- and adjuvant-dependent manner, which plateaued in the highest-dose groups after three injections. In humans, no vaccination-induced anti-huNEO1 IgG responses were detected upon a single immunization, as the values in vaccine and control groups fluctuated around pre-vaccination levels up to 90/360 days post-vaccination. A minority of participants had anti-huNEO1 levels ≥ assay cutoff before vaccination, which did not increase post-vaccination. Thus, despite detecting vaccine-induced huNEO1-specific responses in rabbits, we found no evidence that the candidate vaccine had induced anti-huNEO1 immunity in human adults. The antigen purification process was nevertheless optimized, and haNEO1-reduced vaccines were used in a subsequent Phase 2 trial enrolling 400 non-pregnant women (NCT02956837), in which again no vaccine-induced anti-huNEO1 responses were detected.

A single dose of either 30 µg or 60 µg of nonadjuvanted respiratory syncytial virus prefusion F protein antigen boosts humoral immune responses in women of childbearing age. The investigational vaccine was well tolerated and had a safety profile similar to that of the widely used combined Tdap vaccine., Background Respiratory syncytial virus (RSV) causes bronchiolitis and pneumonia in neonates and infants. RSV vaccination during pregnancy could boost preexisting neutralizing antibody titers, providing passive protection to newborns. Methods Two observer-blinded, controlled studies (RSV F-020 [clinical trials registration NCT02360475] and RSV F-024 [NCT02753413]) evaluated immunogenicity and safety of an investigational RSV vaccine in healthy, nonpregnant 18–45-year-old women. Both studies used a licensed adult formulation of combined tetanus toxoid-diphtheria toxoid-acellular pertussis (Tdap) vaccine as a control. RSV F-020 evaluated immunogenicity and safety: participants were randomized (1:1:1:1) to receive 1 dose of RSV–prefusion F protein (PreF) vaccine containing 30 µg or 60 µg of nonadjuvanted RSV-PreF, 60 µg of aluminum-adjuvanted RSV-PreF, or Tdap. RSV F-024 evaluated safety: participants were randomized 1:1 to receive 1 dose of 60 µg of nonadjuvanted RSV-PreF or Tdap. Results Both studies showed similar reactogenicity profiles for RSV-PreF and Tdap. No serious adverse events were considered vaccine related. In RSV F-020, geometric mean ratios of RSV-A neutralizing antibody levels at day 30 versus prevaccination were 3.1–3.9 in RSV-PreF recipients and 0.9 in controls. Palivizumab-competing antibody concentrations increased >14-fold in RSV-PreF recipients on day 30. RSV antibody titers waned after day 30 but remained well above baseline through day 90. Conclusions All formulations of RSV-PreF boosted preexisting immune responses in 18–45-year old women with comparable immunogenicity. The RSV-PreF safety profile was similar to that of Tdap vaccine.

Background RSV is a common cause of respiratory acute illness in older adults (OA). We evaluated safety and reactogenicity of RSVPreF3 candidate vaccine in young adults (YA) and OA. Methods In this phase I/II, placebo-controlled, multi-country trial (NCT03814590), YA aged 18–40 years were randomized 1:1:1:1 and received 2 doses of Low-, Medium- or High-dose of RSVPreF3 non-adjuvanted vaccine, or placebo, 2 months apart. Following favorable safety evaluation, a staggered enrolment with 2 steps followed in OA aged 60–80 years, who were randomized 1:1:1:1:1:1:1:1:1:1 to receive 1 of the 9 RSV vaccine formulations containing Low-, Medium- or High-dose of RSVPreF3 non-adjuvanted or adjuvanted with AS01E or AS01B, or placebo (same schedule). Safety/reactogenicity up to 1 month post-dose 1 are reported here. Results Exposed set was comprised of 48 YA and 1005 OA. Within 7 days post-dose 1, any solicited/unsolicited adverse event (AE) ranged from 58.3% to 83.3% across YA vaccinees (placebo YA: 58.3%) and from 29.9% to 84.2% across OA vaccinees (placebo OA: 33.7%) (Fig 1). Pain was the most common solicited local AE, being reported in ≤ 58.3% of YA (placebo YA: 0.0%) and at higher rates in the adjuvanted groups (≤ 75.7%) vs non-adjuvanted groups of OA (≤ 14.1%) and placebo OA (4.1%) (Fig 2A). Of solicited general AEs, fatigue (YA: ≤ 41.7% in vaccinees vs 50.0% in placebo; OA: ≤ 48.5% in vaccinees vs 16.3% in placebo) and headache (YA: ≤ 33.3% in vaccinees vs 16.7% in placebo; OA: ≤ 27.7% in vaccinees vs 8.2% in placebo) were most commonly reported (Fig 2B), while fever ≥ 38.0 °C was observed in ≤ 3.0% of OA vaccinees (placebo OA: 0.0%). Grade 3 solicited local and general AEs were observed in OA only, with erythema (≤ 4.9% in vaccinees vs 0.0% in placebo) and fatigue (≤ 2.0% in vaccinees vs 1.0% in placebo) being most common (Fig 2). No serious AEs (SAEs) were reported in YA. A number of 11 OA reported a SAE within 1 month post-dose 1, but none was fatal or assessed as vaccine-related. No clinically significant abnormalities occurred in hematological/biochemical parameters in any group. Figure 1. Percentage of participants presenting at least one type of solicited/unsolicited adverse event (AE) within 7 days post-dose 1 Figure 2. Percentage of participants with at least one type of solicited adverse event (AE) within 7 days post-dose 1 Conclusion First dose of RSVPreF3 candidate vaccine is well tolerated. AE rates tended to be higher after AS01B-adjuvanted formulations compared to other vaccine formulations. No safety concerns were raised. Funding GlaxoSmithKline Biologicals SA Disclosures Jelena Tica, PhD, GSK group of companies (Employee, Shareholder) Javier Ruiz Guiñazú, MD MSc, GSK group of companies (Employee, Shareholder) Charles P. Andrews, MD, GSK group of companies (Scientific Research Study Investigator) Charles Fogarty, MD, GSK group of companies (Grant/Research Support) Edward Kerwin, MD, Amphastar (Consultant, Scientific Research Study Investigator, Advisor or Review Panel member, Speaker’s Bureau)AstraZeneca (Consultant, Scientific Research Study Investigator, Advisor or Review Panel member, Speaker’s Bureau)Boehringer Ingelheim (Consultant, Scientific Research Study Investigator, Advisor or Review Panel member, Speaker’s Bureau)Chiesi (Consultant, Scientific Research Study Investigator, Advisor or Review Panel member, Speaker’s Bureau)Cipla (Consultant, Scientific Research Study Investigator, Advisor or Review Panel member, Speaker’s Bureau)GSK group of companies (Employee, Scientific Research Study Investigator, Advisor or Review Panel member, Speaker’s Bureau)Mylan (Consultant, Scientific Research Study Investigator, Advisor or Review Panel member, Speaker’s Bureau)Novartis (Employee, Advisor or Review Panel member, Research Grant or Support, Speaker’s Bureau)other around 40 pharmaceutical companies (Other Financial or Material Support, conducted multicenter clinical research trials)Pearl (Consultant, Scientific Research Study Investigator, Advisor or Review Panel member, Speaker’s Bureau)Sunovion (Consultant, Scientific Research Study Investigator, Advisor or Review Panel member, Speaker’s Bureau)Theravance (Consultant, Scientific Research Study Investigator, Advisor or Review Panel member, Speaker’s Bureau) Isabel Leroux-Roels, MD PhD, GSK group of companies (Scientific Research Study Investigator) Corinne Vandermeulen, MD PhD, GSK group of companies (Other Financial or Material Support, My university only received Grant/Research Support) Marie-Pierre David, MSc, GSK group of companies (Employee, Shareholder) Nancy Dezutter, PhD, PharmD, RPh, GSK group of companies (Employee, Shareholder) Laurence Fissette, MSc, GSK group of companies (Employee) Juliane Koch, MD, GSK group of companies (Employee, Shareholder) Narcisa Mesaros, MD, MSc, GSK group of companies (Employee)

Background. Respiratory syncytial virus (RSV) is a leading cause of childhood bronchiolitis and pneumonia, particularly in early infancy. Immunization of pregnant women could boost preexisting immune responses, providing passive protection to newborns through placental transfer of anti-RSV antibody. Methods. In this first-in-humans clinical trial of a purified recombinant RSV protein F vaccine engineered to preferentially maintain prefusion conformation (RSV-PreF), 128 healthy men 18–44 years old were randomized to one dose of a RSV-PreF vaccine containing 10, 30, or 60 µg of RSV-PreF antigen, with or without alum adjuvant, or control, and followed for one year for safety and immunogenicity outcomes. Results. Injection site pain was the most common adverse event, reported by up to 81.3% of participants. The highest RSV neutralizing antibody responses were in the 30 µg RSV-PreF/alum, 60 µg RSV-PreF/alum, and 60 µg RSV-PreF/nonadjuvant groups. Responses were evident on day 7, and 30 days after vaccination these participants had RSV-A neutralizing antibody titers of ≥1:512, and >70% had titers of 1:1024, with titers increasing by 3.2–4.9 fold. Responses remained high on day 60 but waned on days 180 and 360. Conclusions. The RSV-PreF vaccine elicited rapid RSV neutralizing antibody responses in healthy young men, with an acceptable adverse event profile.

Immunogenicity and safety of different adjuvants combined with a model antigen (HBsAg) were compared. Healthy HBV-naïve adults were randomized to receive HBs adjuvanted with alum or Adjuvant Systems AS01B, AS01E, AS03A or AS04 at Days 0 and 30. Different frequencies of HBs-specific CD4. + T cells 14 days post dose 2 but similar polyfunctionality profiles were induced by the different adjuvants with frequencies significantly higher in the AS01B and AS01E groups than in the other groups. Antibody concentrations 30 days post-dose 2 were significantly higher in AS01B, AS01E and AS03A than in other groups. Limited correlations were observed between HBs-specific CD4. + T cell and antibody responses. Injection site pain was the most common solicited local symptom and was more frequent in AS groups than in alum group. Different adjuvants formulated with the same antigen induced different adaptive immune responses and reactogenicity patterns in healthy naïve adults. The results summary for this study (GSK study number 112115 - NCT, SCOPUS: ar.j, info:eu-repo/semantics/published

Long-term immunity, evaluated by the persistence of antibody titers, is important to assess duration of protection induced by vaccination. This paper aims at drawing awareness on the risk of misinterpreting persistence results in absence of adjustment for missing or left-censored data. Using simulations, the paper shows that repeated measurement models are an appropriate alternative to control the bias associated to unadjusted persistence results.

This phase II study evaluated the effect of chloroquine on the specific CD8 + T-cell responses to and the safety of a booster dose of investigational human immunodeficiency virus type 1 (HIV-1) F4/AS01 B vaccine containing 10 μg of recombinant fusion protein (F4) adjuvanted with the AS01 B adjuvant system. Healthy adults aged 21 to 41 years, primed 3 years before with two F4/AS01 B doses containing 10 or 30 μg of F4 ( ClinicalTrials.gov registration number NCT00434512), were randomized (1:1) to receive the F4/AS01 B booster administered alone or 2 days after chloroquine (300 mg). F4-specific CD8 + /CD4 + T-cell responses were characterized by intracellular cytokine staining and lymphoproliferation assays and anti-F4 antibodies by enzyme-linked immunosorbent assays (ELISAs). No effect of chloroquine on CD4 + /CD8 + T-cell and antibody responses and no vaccine effect on CD8 + T-cell responses (cytokine secretion or proliferation) were detected following F4/AS01 B booster administration. In vitro , chloroquine had a direct inhibitory effect on AS01 B adjuvant properties; AS01-induced cytokine production decreased upon coincubation of cells with chloroquine. In the pooled group of participants primed with F4/AS01 B containing 10 μg of F4, CD4 + T-cell and antibody responses induced by primary vaccination persisted for at least 3 years. The F4/AS01 B booster induced strong F4-specific CD4 + T-cell responses, which persisted for at least 6 months with similar frequencies and polyfunctional phenotypes as following primary vaccination, and high anti-F4 antibody concentrations, reaching higher levels than those following primary vaccination. The F4/AS01 B booster had a clinically acceptable safety and reactogenicity profile. An F4/AS01 B booster dose, administered alone or after chloroquine, induced robust antibody and F4-specific CD4 + T-cell responses but no significant CD8 + T-cell responses (cytokine secretion or proliferation) in healthy adults. (This study has been registered at ClinicalTrials.gov under registration number NCT00972725).

This open, randomized clinical trial (NCT00758264) evaluated the coadministration of a booster dose of the 10-valent pneumococcal conjugate vaccine (PHiD-CV) and a single dose of the tetravalent meningococcal conjugate vaccine (MenACWY-TT) in Taiwanese and Mexican toddlers.Healthy toddlers aged 12-23 months (N = 363) were randomized (2:1:1) to receive either both vaccines at first visit, MenACWY-TT at first visit and 1 month later PHiD-CV, or PHiD-CV at first visit and 1 month later MenACWY-TT. Immune responses were measured 1 month after MenACWY-TT vaccination by meningococcal serum bactericidal activity (rSBA) assay and 1 month after PHiD-CV vaccination by pneumococcal 22F-inhibition enzyme-linked immunosorbent assay and functional opsonophagocytic activity assay. Solicited and unsolicited symptoms were recorded for days 4 and 31 postvaccination, respectively. Serious adverse events were recorded throughout the study.The prespecified criteria for noninferiority of coadministration versus individual administrations were met for all meningococcal serogroups (in terms of percentages of toddlers with rSBA titer ≥8) and all vaccine pneumococcal serotypes (in terms of antibody geometric mean concentration ratios), except pneumococcal serotype 18C. For each meningococcal serogroup, ≥97.5% of toddlers across the 3 groups had rSBA titers ≥128 at 1 month after MenACWY-TT vaccination. For each pneumococcal serotype, at 1 month after PHiD-CV vaccination, ≥96.0% and ≥92.9% of toddlers across the 3 groups had antibody concentrations ≥0.2 µg/mL and opsonophagocytic activity titers ≥8, respectively. The safety profiles of both vaccines when coadministered were clinically acceptable.This study supports the coadministration of PHiD-CV and MenACWY-TT in toddlers.