Phase 1 Safety and Immunogenicity Study of a Respiratory Syncytial Virus Vaccine With an Adenovirus 26 Vector Encoding Prefusion F (Ad26.RSV.preF) in Adults Aged ≥60 Years

2020 ◽  
Vol 222 (6) ◽  
pp. 979-988 ◽  
Author(s):  
Kristi Williams ◽  
Arangassery Rosemary Bastian ◽  
Robert Allen Feldman ◽  
Edmund Omoruyi ◽  
Els de Paepe ◽  
...  
Keyword(s):  
Older Adults ◽  
Respiratory Syncytial Virus ◽  
Adverse Events ◽  
Immune Responses ◽  
Phase 1 ◽  
Geometric Mean ◽  
High Dose ◽  
Serious Adverse Events ◽  
Syncytial Virus ◽  
Vector Particles

Abstract Background Despite the high disease burden of respiratory syncytial virus (RSV) in older adults, there is no approved vaccine. We evaluated the experimental RSV vaccine, Ad26.RSV.preF, a replication-incompetent adenovirus 26 vector encoding the F protein stabilized in prefusion conformation. Methods This phase 1 clinical trial was performed in healthy adults aged ≥60 years. Seventy-two participants received 1 or 2 intramuscular injections of low-dose (LD; 5 × 1010 vector particles) or high-dose (HD; 1 × 1011 vector particles) Ad26.RSV.preF vaccine or placebo, with approximately 12 months between doses and 2-year follow-up for safety and immunogenicity outcomes. Results Solicited adverse events were reported by 44% of vaccine recipients and were transient and mild or moderate in intensity. No serious adverse events were related to vaccination. After the first vaccination, geometric mean titers for RSV-A2 neutralization increased from baseline (432 for LD and 512 for HD vaccine) to day 29 (1031 for LD and 1617 for HD). Pre-F–specific antibody geometric mean titers and median frequencies of F-specific interferon γ–secreting T cells also increased substantially from baseline. These immune responses were still maintained above baseline levels 2 years after immunization and could be boosted with a second immunization at 1 year. Conclusions Ad26.RSV.preF (LD and HD) had an acceptable safety profile and elicited sustained humoral and cellular immune responses after a single immunization in older adults.

scholarly journals Immunogenicity and Safety of 3 Formulations of a Respiratory Syncytial Virus Candidate Vaccine in Nonpregnant Women: A Phase 2, Randomized Trial

2019 ◽  
Vol 220 (11) ◽  
pp. 1816-1825 ◽  
Author(s):  
Tino F Schwarz ◽  
Roderick A McPhee ◽  
Odile Launay ◽  
Geert Leroux-Roels ◽  
Jaak Talli ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Neutralizing Antibodies ◽  
Geometric Mean ◽  
Neutralizing Antibody ◽  
Candidate Vaccine ◽  
Phase 2 ◽  
Serious Adverse Events ◽  
Intramuscular Dose ◽  
Syncytial Virus ◽  
Neonates And Infants

Abstract Background Respiratory syncytial virus (RSV) is a common cause of respiratory tract illness and hospitalization in neonates and infants. RSV vaccination during pregnancy may protect offspring in their first months of life. Methods This randomized, observer-blind, multicenter, phase 2 study evaluated the immunogenicity and safety of an RSV candidate vaccine in healthy nonpregnant women aged 18–45 years. Four hundred participants were randomized (1:1:1:1) to receive a single intramuscular dose of vaccine containing 30 µg, 60 µg, or 120 µg of RSV fusion protein engineered to preferentially maintain a prefusion conformation (RSV-PreF vaccine) or placebo. Results Thirty days postvaccination, RSV-A neutralizing antibody geometric mean titers (GMTs) increased 3.75-, 4.42- and 4.36-fold; RSV-B neutralizing antibody GMTs 2.36-, 2.54- and 2.76-fold; and palivizumab competing antibody (PCA) concentrations 11.69-, 14.38- and 14.24-fold compared with baseline levels in the 30 µg, 60 µg, and 120 µg RSV-PreF groups, respectively. Antibody titers and PCA concentrations at day 30 were significantly higher with the 120 µg compared to the 30 µg RSV-PreF vaccine. All RSV-PreF vaccine formulations and the placebo had similar reactogenicity profiles. No serious adverse events were considered to be related to the RSV-PreF vaccine. Conclusions The 3 formulations of the investigational RSV-PreF vaccine were well-tolerated and induced RSV-A and RSV-B neutralizing antibodies and PCAs in healthy, nonpregnant women. Clinical Trials Registration NCT02956837.

scholarly journals A first-in-human evaluation of the safety and immunogenicity of SCB-2019, an adjuvanted, recombinant SARS-CoV-2 trimeric S-protein subunit vaccine for COVID-19 in healthy adults; a phase 1, randomised, double-blind, placebo-controlled trial

2020 ◽  
Author(s):  
Peter Richmond ◽  
Lara Hatchuel ◽  
Min Dong ◽  
Brenda Ma ◽  
Branda Hu ◽  
...  
Keyword(s):  
Older Adults ◽  
Immune Responses ◽  
Subunit Vaccine ◽  
Phase 1 ◽  
Intracellular Cytokine Staining ◽  
High Dose ◽  
Protein Subunit ◽  
Neutralising Antibodies ◽  
S Protein ◽  
Human Dose

ABSTRACTBackgroundAs part of the accelerated development of prophylactic vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) we report a first-in-human dose-finding and adjuvant justification study of SCB-2019, a novel protein subunit vaccine candidate composed of a stabilised trimeric form of the spike (S)-protein produced in CHO-cells, combined with two different adjuvants.MethodsThis phase 1 study was done in one centre in Western Australia in 151 healthy adult volunteers in two age groups (18–54 and 55–75 years), allocated to 15 groups (nine young and six older adults) to receive two doses, 21 days apart, of placebo, or 3 μg, 9 μg or 30 μg SCB-2019, alone or adjuvanted with AS03 or CpG/Alum. Reactogenicity was assessed for 7 days after each vaccination. Humoral responses were measured as SCB-2019 binding and ACE2-competitive binding IgG antibodies by ELISA, and as neutralising antibodies by wild-type SARS-CoV-2 microneutralisation assay; cellular responses to pooled S-protein peptides were measured by flow-cytometric intracellular cytokine staining.FindingsWe report on 148 participants with at least 4 weeks follow-up post dose 2. Three participants withdrew, two for personal reasons and one with an unrelated SAE (pituitary adenoma). Vaccination was well tolerated, with few Grade 3 solicited adverse events (AE). Most local AEs were mild injection site pain, which were more frequent with formulations containing AS03 than CpG/Alum or unadjuvanted SCB-2019. Systemic AEs, mostly transient headache, fatigue or myalgia, were more frequent in young adults than older adults after the first dose, but similar after second doses. Unadjuvanted SCB-2019 elicited minimal immune responses, but SCB-2019 with fixed doses of AS03 or CpG/Alum induced high titres and seroconversion rates of binding and neutralising antibodies in both young and older adults. Titres were higher than those observed in a panel of COVID-19 convalescent sera in all AS03 groups and high dose CpG/Alum groups. Both adjuvanted formulations elicited Th1-biased CD4+ T cell responses.InterpretationSCB-2019 trimeric protein formulated with AS03 or CpG/Alum adjuvants elicited robust humoral and cellular immune responses against SARS-CoV-2 with high viral neutralising activity. Both adjuvanted formulations were well tolerated and are suitable for further clinical development.Clinical trial registrationClinicalTrials.gov identifier NCT04405908.

scholarly journals Serious Adverse Events in the Canadian Registry of Children Receiving Palivizumab (CARESS) for Respiratory Syncytial Virus Prevention

PLoS ONE ◽  
2015 ◽  
Vol 10 (8) ◽  
pp. e0134711 ◽  
Author(s):  
Jinghan Jenny Chen ◽  
Parco Chan ◽  
Bosco Paes ◽  
Ian Mitchell ◽  
Abby Li ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Adverse Events ◽  
Serious Adverse Events ◽  
Syncytial Virus

scholarly journals Dose Selection for an Adjuvanted Respiratory Syncytial Virus F Protein Vaccine for Older Adults Based on Humoral and Cellular Immune Responses

2017 ◽  
Vol 24 (9) ◽  
Author(s):  
Judith Falloon ◽  
H. Keipp Talbot ◽  
Craig Curtis ◽  
John Ervin ◽  
Diane Krieger ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Immune Responses ◽  
Phase 1 ◽  
Second Phase ◽  
Double Blind Study ◽  
Protein Vaccine ◽  
Double Blind ◽  
Cellular Immune Responses ◽  
Syncytial Virus ◽  
Cellular Immune

ABSTRACT This is the second phase 1 study of a respiratory syncytial virus (RSV) vaccine containing RSV fusion protein (sF) adjuvanted with glucopyranosyl lipid A (GLA) in a squalene-based 2% stable emulsion (GLA-SE). In this randomized, double-blind study, 261 subjects aged ≥60 years received inactivated influenza vaccine (IIV), a vaccine containing 120 μg sF with escalating doses of GLA (1, 2.5, or 5 μg) in SE, or a vaccine containing 80 μg sF with 2.5 μg GLA in SE. Subjects receiving 120 μg sF with 2.5 or 5 μg GLA were also randomized to receive IIV or placebo. Immunity to RSV was assessed by detection of microneutralizing, anti-F immunoglobulin G, and palivizumab-competitive antibodies and F-specific gamma interferon enzyme-linked immunosorbent spot assay T-cell responses. Higher adjuvant doses increased injection site discomfort, but at the highest dose, the reactogenicity was similar to that of IIV. Significant humoral and cellular immune responses were observed. The 120 μg sF plus 5.0 μg GLA formulation resulted in the highest responses in all subjects and in older subjects. These results confirm previous observations of vaccine tolerability, safety, and immunogenicity and were used to select the 120 μg sF plus 5.0 μg GLA formulation for phase 2 evaluation. (This study has been registered at ClinicalTrials.gov under registration no. NCT02289820.)

scholarly journals Viral Shedding and Immune Responses to Respiratory Syncytial Virus Infection in Older Adults

2013 ◽  
Vol 207 (9) ◽  
pp. 1424-1432 ◽  
Author(s):  
Edward E. Walsh ◽  
Derick R. Peterson ◽  
Aja E. Kalkanoglu ◽  
Frances Eun-Hyung Lee ◽  
Ann R. Falsey
Keyword(s):  
Older Adults ◽  
Respiratory Syncytial Virus ◽  
Virus Infection ◽  
Immune Responses ◽  
Respiratory Syncytial Virus Infection ◽  
Viral Shedding ◽  
Syncytial Virus

scholarly journals First-in-Human Trial of a Recombinant Stabilized Prefusion SARS-CoV-2 Spike Protein Vaccine with Adjuvant of Aluminum Hydroxide and CpG 1018

2021 ◽  
Author(s):  
Szu-Min Hsieh ◽  
Wang-Da Liu ◽  
Yu-Shan Huang ◽  
Yi-Jiun Lin ◽  
Erh-Fang Hsieh ◽  
...  
Keyword(s):  
Adverse Events ◽  
Aluminum Hydroxide ◽  
Phase 1 ◽  
Geometric Mean ◽  
Laboratory Data ◽  
Spike Protein ◽  
High Dose ◽  
Protein Vaccine ◽  
Open Label ◽  
Mean Values

Design This is a phase 1, dose-escalation open-label trial to evaluate the safety and immunogenicity of MVC-COV1901, a recombinant stabilized prefusion SARS-CoV-2 spike (S-2P) protein vaccine with adjuvant of aluminum hydroxide and CpG 1018. Methods We enrolled 45 healthy adults from 20 to 49 years of age to be administered with two vaccinations of MVC-COV1901 in a low dose (LD), middle dose (MD), and high dose (HD) of spike protein at 28 days apart. There were 15 participants in each dose group, and all of them were followed up for 28 days after the second vaccination at the time of interim analysis. Adverse events (AEs) and laboratory data were recorded for safety evaluation. Blood samples were collected for wild-type SARS-CoV-2 and pseudovirus neutralization assays as well as SARS-CoV-2 spike-specific immunoglobulin G (IgG) at various times. Overall, the study duration will be 7 months. Results Solicited events were mostly mild and similar in the participants of all three dose groups. No subject experienced fever. There were no serious nor adverse events of special interest at the time point of this interim report. After the second vaccination, the SARS-CoV-2 spike specific IgG titers increased with peak geometric mean titers at 7178.245 (LD), 7746.086 (MD), and 11220.58 (HD), respectively. Serum neutralizing activity was detected by two methods in all participants of MD and HD groups, with geometric mean values generally comparable to those of a panel of control convalescent serum specimens. All of the participants in the MD and HD groups were seroconverted after the second vaccination. Conclusions The MVC-COV1901 vaccine is safe and elicits remarkable immune responses especially in the MD and HD groups.

scholarly journals Phase 1 Assessment of the Safety and Immunogenicity of an mRNA- Lipid Nanoparticle Vaccine Candidate Against SARS-CoV-2 in Human Volunteers

2020 ◽  
Author(s):  
Peter Kremsner ◽  
Philipp Mann ◽  
Jacobus Bosch ◽  
Rolf Fendel ◽  
Julian J. Gabor ◽  
...  
Keyword(s):  
Adverse Events ◽  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Clinical Investigation ◽  
Phase 1 ◽  
Fold Increase ◽  
Serious Adverse Events ◽  
S Protein ◽  
Human Volunteers ◽  
Dose Dependent

ABSTRACTThere is an urgent need for vaccines to counter the COVID-19 pandemic due to infections with severe acute respiratory syndrome coronavirus (SARS-CoV-2). Evidence from convalescent sera and preclinical studies has identified the viral Spike (S) protein as a key antigenic target for protective immune responses. We have applied an mRNA-based technology platform, RNActive®, to develop CVnCoV which contains sequence optimized mRNA coding for a stabilized form of S protein encapsulated in lipid nanoparticles (LNP). Following demonstration of protective immune responses against SARS-CoV-2 in animal models we performed a dose-escalation phase 1 study in healthy 18-60 year-old volunteers.This interim analysis shows that two doses of CVnCoV ranging from 2 μg to 12 μg per dose, administered 28 days apart were safe. No vaccine-related serious adverse events were reported. There were dose-dependent increases in frequency and severity of solicited systemic adverse events, and to a lesser extent of local reactions, but the majority were mild or moderate and transient in duration. Immune responses when measured as IgG antibodies against S protein or its receptor-binding domain (RBD) by ELISA, and SARS-CoV-2-virus neutralizing antibodies measured by micro-neutralization, displayed dose-dependent increases. Median titers measured in these assays two weeks after the second 12 μg dose were comparable to the median titers observed in convalescent sera from COVID-19 patients. Seroconversion (defined as a 4-fold increase over baseline titer) of virus neutralizing antibodies two weeks after the second vaccination occurred in all participants who received 12 μg doses.Preliminary results in the subset of subjects who were enrolled with known SARS-CoV-2 seropositivity at baseline show that CVnCoV is also safe and well tolerated in this population, and is able to boost the pre-existing immune response even at low dose levels.Based on these results, the 12 μg dose is selected for further clinical investigation, including a phase 2b/3 study that will investigate the efficacy, safety, and immunogenicity of the candidate vaccine CVnCoV.

scholarly journals SARS-CoV-2 DNA Vaccine INO-4800 Induces Durable Immune Responses Capable of Being Boosted in a Phase 1 Open-Label Trial

2021 ◽  
Author(s):  
Kimberly A Kraynyak ◽  
Elliott Blackwood ◽  
Joseph Agnes ◽  
Pablo Tebas ◽  
Mary Giffear ◽  
...  
Keyword(s):  
T Cells ◽  
Adverse Events ◽  
Immune Responses ◽  
Dna Vaccine ◽  
Booster Dose ◽  
Phase 1 ◽  
The Elderly ◽  
Open Label ◽  
Serious Adverse Events ◽  
Primary Series

Background: Additional SARS-CoV-2 vaccines that are safe and effective as both primary series and booster remain urgently needed to combat the COVID-19 pandemic. Here we describe the safety and durability of the immune response from two doses of a DNA vaccine (INO-4800) targeting the full-length Spike antigen and a subsequent homologous booster dose. Methods: INO-4800 was evaluated in 120 healthy participants across three dose groups (0.5 mg, 1.0 mg and 2.0 mg), each stratified by age. INO-4800 was injected intradermally followed by electroporation at 0 and 4 weeks followed by an optional booster dose 6-10.5 months following the second dose. Results: INO-4800 was well-tolerated, with no treatment-related serious adverse events reported. Most adverse events were mild in severity and did not increase in frequency with age and subsequent dosing. A durable antibody response was observed 6 months following the second dose; a homologous booster dose significantly increased immune responses. Cytokine producing T cells and activated CD8+T cells with lytic potential were detected in the 2.0 mg dose group. Conclusion: INO-4800 was well-tolerated as a 2-dose series and as a homologous booster dose in all adults, including the elderly. These results support further development of INO-4800 as a primary series and as a booster. Keywords: SARS-CoV-2; Clinical trial; DNA Vaccine; COVID-19; Immunogenicity; Booster

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