Evolving Horizons: Adenovirus Vectors’ Timeless Influence on Cancer, Gene Therapy and Vaccines

Viruses, Journal Year: 2023, Volume and Issue: 15(12), P. 2378 - 2378

Published: Dec. 3, 2023

Efficient and targeted delivery of a DNA payload is vital for developing safe gene therapy. Owing to the recent success commercial oncolytic vector multiple COVID-19 vaccines, adenovirus vectors are back in spotlight. Adenovirus can be used therapy by altering wild-type virus making it replication-defective; specific viral genes removed replaced with segment that holds therapeutic gene, this as vehicle tissue delivery. Modified conditionally replicative–oncolytic adenoviruses target tumors exclusively have been studied clinical trials extensively. This comprehensive review seeks offer summary vectors, exploring their characteristics, genetic enhancements, diverse applications preclinical settings. A significant emphasis placed on crucial role advancing cancer latest breakthroughs vaccine various diseases. Additionally, we tackle current challenges future avenues optimizing promising open new frontiers fields cell therapies.

Language: Английский

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SCB-2019 protein vaccine as heterologous booster of neutralizing activity against SARS-CoV-2 Omicron variants after immunization with other COVID-19 vaccines

Human Vaccines & Immunotherapeutics, Journal Year: 2024, Volume and Issue: 20(1)

Published: Jan. 11, 2024

We assessed the non-inferiority of homologous boosting compared with heterologous recombinant protein vaccine, SCB-2019, in adults previously immunized different COVID-19 vaccines. Three equal cohorts (N ~ 420) Philippino (18-80 years) Comirnaty, CoronaVac or Vaxzevria vaccines were randomized 1:1 to receive (SCB-2019) boosters. Neutralizing antibodies against prototype SARS-CoV-2 (Wuhan-Hu-1) measured all participants and Delta variant Omicron sub-lineages subsets (30‒50 per arm) 15 days after boosting. Participants recorded solicited adverse events for 7 unsolicited serious until Day 60. Prototype neutralizing responses on SCB-2019 statistically non-inferior boosters, superior CoronaVac, but lower than Comirnaty. BA.1, BA.2, BA.4 BA.5 variants higher Vaxzevria, Responses BF.7, BQ.1.1.3, XBB1.5 following Comirnaty booster significantly booster. reactogenicity was similar Comirnaty; most frequent mild/moderate injection site pain, headache fatigue. No vaccine-related reported. Heterologous well tolerated elicited tested SARS-COV-2 viruses including BA.4, BA.5, that not

Language: Английский

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Concurrent Administration of COVID-19 and Influenza Vaccines Enhances Spike-Specific Antibody Responses

Open Forum Infectious Diseases, Journal Year: 2024, Volume and Issue: 11(4)

Published: March 13, 2024

Abstract Background The bivalent COVID-19 mRNA boosters became available in fall 2022 and were recommended alongside the seasonal influenza vaccine. However, immunogenicity of concurrent vs separate administration these vaccines remains unclear. Methods Here, we analyzed antibody responses health care workers who received booster vaccine on same day or different days through systems serology. Antibody-binding functional characterized at peak after 6 months following vaccination. Results IgG1 neutralization to SARS-CoV-2 XBB.1.5 higher as compared with vaccines. While similar results not observed for responses, no interference was noted administration. Conclusions These data suggest that may yield more durable neutralizing while maintaining against influenza.

Language: Английский

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Safety and immunogenicity of Ad5-nCoV immunization after three-dose priming with inactivated SARS-CoV-2 vaccine in Chinese adults

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Aug. 8, 2023

Data on the safety and immunity of a heterologous booster (fourth dose) after three-doses inactivated SARS-CoV-2 vaccine in Chinese adults are limited. We evaluate immunogenicity Ad5-nCoV randomized, double-blind, parallel-controlled phase 4 clinical trial Zhejiang, China (NCT05373030). Participants aged 18-80 years (100 per group), administered three doses ≥6 months earlier, enrolled randomized 1:1 into two groups, which intramuscular or (CoronaVac Covilo). All observed adverse reactions predictable manageable. elicits significantly higher RBD-specific IgG levels, with geometric mean concentration 2924.0 day 14 post-booster, 7.8-fold that vaccine. Pseudovirus-neutralizing antibodies to Omicron BA.4/5 show similar pattern, titers 228.9 group 65.5 group. maintains high antibody levels 90, seroconversion 71.4%, while is 5.2%, almost pre-booster levels. A fourth vaccination following immunogenic, tolerable, more efficient than stronger humoral response against for longer homologous boosting.

Language: Английский

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Boosting with adjuvanted SCB-2019 elicits superior Fcγ-receptor engagement driven by IgG3 to SARS-CoV-2 spike

npj Vaccines, Journal Year: 2024, Volume and Issue: 9(1)

Published: Jan. 5, 2024

Abstract With the continued emergence of variants concern, global threat COVID-19 persists, particularly in low- and middle-income countries with limited vaccine access. Protein-based vaccines, such as SCB-2019, can be produced on a large scale at low cost while antigen design adjuvant use modulate efficacy safety. While effective humoral immunity against SARS-CoV-2 has been shown to depend both neutralization Fc-mediated immunity, data effectiveness protein-based vaccines enhanced is limited. Here, we assess profile, including antibody isotypes, subclasses, Fc receptor binding generated by boosting recombinant trimer-tag protein SCB-2019. Individuals who were primed 2 doses ChAdOx1 equally divided into 4 groups boosted following formulations: Group 1: 9 μg SCB-2019 Alhydrogel; 2: CpG 1018, 3: 30 4: ChAdOx1. 3 showed FcγR wild-type compared Groups 1 2, showing dose-dependent enhancement conferred vaccine. Moreover, from day 15 after vaccination, exhibited higher IgG3 across concerns, Omicron its subvariants, ChAdOx1-boosted individuals. Overall, this highlights potential cost-efficient regimen concerns.

Language: Английский

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Safety and immunogenicity of SCB-2019, an adjuvanted, recombinant SARS-CoV-2 trimeric S-protein subunit COVID-19 vaccine in healthy 12–17 year-old adolescents

Human Vaccines & Immunotherapeutics, Journal Year: 2023, Volume and Issue: 19(1)

Published: Jan. 2, 2023

We previously demonstrated the efficacy of COVID-19 vaccine candidate, SCB-2019, in adults SPECTRA phase 2/3 study. extended study to include 1278 healthy 12–17-year-old adolescents Belgium, Colombia, and Philippines who received either two doses SCB-2019 or placebo 21 days apart, assess immunogenicity as neutralizing antibodies against prototype SARS-CoV-2 variants concern, safety reactogenicity solicited unsolicited adverse events with a comparator group young (18–25 years). In participants no evidence prior infection was non-inferior that adults; respective geometric mean titers (GMT) 14 after second vaccination were 271 IU/mL (95% CI: 211–348) 144 (116–178). Most (1077, 84.3%) had serologic SAR-CoV-2 exposure at baseline; these seropositive GMTs increased from 173 (135–122) 982 (881–1094) dose. Neutralizing Delta Omicron BA also increased, most notably those exposure. well tolerated generally mild moderate, transient comparable adolescent groups except for injection site pain – reported 20% 7.3% injections. highly immunogenic adolescents, especially exposure, adults. Clinical trial registration: EudraCT 2020–004272–17; ClinicalTrials.gov NCT04672395.

Language: Английский

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Superior Boosting of Neutralizing Titers Against Omicron SARS-CoV-2 Variants by Heterologous SCB-2019 Vaccine vs a Homologous Booster in CoronaVac-Primed Adults

The Journal of Infectious Diseases, Journal Year: 2023, Volume and Issue: 228(9), P. 1253 - 1262

Published: July 13, 2023

Abstract Background We compared homologous and heterologous boosting in adults the Philippines primed with 2 or 3 doses of CoronaVac, recombinant protein vaccine, SCB-2019. Methods CoronaVac-immunized (18–72 years) received a full half dose SCB-2019 booster. assessed all neutralizing antibody (NAb) responses against prototype SARS-CoV-2 after 15 days NAb Delta Omicron variants subsets (30‒50 per arm). Participants recorded adverse events. Results In 2-dose CoronaVac-primed geometric mean titers (GMT) were 203 IU/mL (95% confidence interval [CI], 182–227) 939 CI, 841–1049) CoronaVac boosters; GMT ratio (4.63; 95% 3.95–5.41) met predefined noninferiority post-hoc superiority criteria. After 3-dose CoronaVac-priming GMTs 279 240–325), 1044 898–1213), 668 520–829) following half-dose boosters, respectively. ratios comparing greater than 2. Mild to moderate reactogenicity was evenly balanced between groups. No vaccine-related serious events reported. Conclusions Full boosters well tolerated superior immunogenicity particularly newly emerged variants. Clinical Trials Registration. NCT05188677.

Language: Английский

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Interchangeability of different COVID-19 vaccine platforms as booster doses: A phase 3 study mimicking real-world practice

Vaccine, Journal Year: 2024, Volume and Issue: 42(19), P. 3989 - 3998

Published: May 17, 2024

The COVID-19 pandemic is over but the highly immunized or naturally exposed global population still requires booster vaccinations against newly emerging SARS-CoV-2 variants. We assessed safety and immunogenicity of doses vaccines based on three different platforms in a setting that mimics current routine practice Brazil. In this phase 3 study from 14 February 2023 to 12 June we enrolled previously adults receive an additional dose one vaccines. Immunogenicity ancestor Omicron BF.7, BQ.1.1.3, XBB.1.5.6 sub-lineages was measured as ELISA IgG virus neutralizing (VNT) antibodies safety/reactogenicity using diary cards. Volunteers with history full primary immunization striated cohorts according their previous vaccination history—0 (n = 26), 1 140) 2 606) vaccinations—were randomized 2:1:1 either recombinant protein (SCB-2019, Clover), adenovirus-vector (ChAdOx1-S, AstraZeneca/Fiocruz), mRNA (BNT162b2, Pfizer/Wyeth). Baseline antibody titers were higher individuals who had received two boosters both increased all groups regardless number vaccine used. Day 28 geometric mean (GMTs) mean-fold rises (GMFR) variants after BNT162b than SCB-2019 ChAdOx1-S, displayed more rapid waning at 84. Within each elicited similar GMFR strains. All well tolerated solicited reactogenicity profiles. Protein, equally immunogenic fully primed 0–2 prior boosters. induced highest immune responses also most months vaccination. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT05812586.

Language: Английский

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A two-arm analysis of the immune response to heterologous boosting of inactivated SARS-CoV-2 vaccines

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: Oct. 31, 2023

Several vaccine programs were introduced during the COVID-19 pandemic, which included inactivated virus, DNA viral vectors and mRNA vaccines. Booster are recommended, especially for those in high-risk groups. However, many of these booster involve heterologous This study enrolled volunteers who first received two full-dose CoronaVac vaccinations before receiving boosters with DNA- and/or mRNA-vaccines an additional 2 doses (n = 40) or 3 16). Our results showed no difference side effects, neutralizing antibodies, T-cell responses any vaccination programs. capacity IFN-γ against Omicron variant 4 5 improved. Polarization peripheral memory T cells after stimulation all groups peptide increased trend naïve central phenotypes both CD4+ CD8+ cells, suggesting that exposure to antigens will drive into a lymphoid resident cell phenotype. data support continuous program maximize effectiveness immunity, people at high risk. Furthermore, number boosting is important maintaining immunity.

Language: Английский

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Safety and immunogenicity of SCB-2019, an adjuvanted, recombinant SARS-CoV-2 trimeric S-protein subunit COVID-19 vaccine in healthy 12–17 year-old adolescents

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Feb. 26, 2023

ABSTRACT We previously demonstrated efficacy of the COVID-19 vaccine candidate, SCB-2019, in adults SPECTRA phase 2/3 study. extended study to include 1278 healthy 12–17-year-old adolescents Belgium, Colombia and Philippines who received either two doses SCB-2019 or placebo 21 days apart, assess immunogenicity as neutralizing antibodies against prototype SARS-CoV-2 variants concern, safety reactogenicity solicited unsolicited adverse events with a comparator group young (18–25 years). In participants no evidence prior infection was non-inferior that adults; respective geometric mean titers (GMT) 14 after second vaccination were 271 IU/mL (95% CI: 211–348) 144 (116–178). Most (1077, 84.3%) had serologic SAR-CoV-2 exposure at baseline; these seropositive GMTs increased from 173 (135–122) 982 (881–1094) dose. Neutralizing Delta Omicron BA also increased, most notably those exposure. well tolerated generally mild moderate, transient comparable adolescent groups except for injection site pain – reported 20% 7.3% injections. highly immunogenic adolescents, especially exposure, adults. Clinical trial registration EudraCT 2020-004272-17; ClinicalTrials.gov NCT04672395 .

Language: Английский

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