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1.
Vaccine ; 42(22): 126223, 2024 Sep 17.
Article in English | MEDLINE | ID: mdl-39151232

ABSTRACT

Objectives We evaluated the safety, immunogenicity and efficacy of Abdala, a protein subunit vaccine for 2019 coronavirus disease (COVID-19), in children and adolescents. Methods A phase 2, open-label, single-arm clinical trial was carried out. Subjects aged 3 to 18 years were eligible. Abdala vaccine was administered intramuscularly at 0-14-28 days. The main endpoints were safety and the immunobridging analysis with a non-inferiority design, to infer the efficacy of the vaccine in paediatric population based on the comparison of neutralizing antibodies (NAb) to SARS-CoV-2, with adults (19-21 years). The trial is registered with the Cuban Public Registry of Clinical Trials, RPCEC00000390. Results From September 13th to September 17th, 2021, 703 participants were included in the context of a predominantly SARS-CoV-2 Delta variant circulation. The number of individuals who experienced adverse reactions was 264/703 (37·6%). Adverse reactions were mostly mild and occurred at the injection site, which resolved within the first 24-48 h. There were no reports of severe adverse events. For the non-inferiority comparison of 297 children (3-11 years) with 297 adults, the geometric mean (GMT) ratio of SARS-CoV-2 NAb was 0·87 (95% CI 0·69-1·08) and 1·07 (0·82-1·39) in the same comparison for 203 adolescents (12-18 years) and 203 adults. For both age groups, the lower limit of GMT was higher than 0·67. The differences in seroresponse rates of Nab for children were 1% (-2%, 4%) and -3% (-7%, 1%) for adolescents, higher than -10% in both age groups. Conclusions The Abdala vaccine was safe and immunogenic in a paediatric population aged 3-18 years, with inferred efficacy based on non-inferior analysis. The vaccine is very suitable to fit into massive vaccination strategies, considering the advantages of using the same vaccine strength (RBD 50 µg) and schedule of administration for both adults and children, as well as the easy storage and handling conditions at 2-8 °C.


Subject(s)
Antibodies, Neutralizing , Antibodies, Viral , COVID-19 Vaccines , COVID-19 , SARS-CoV-2 , Vaccines, Subunit , Humans , Adolescent , Child , COVID-19 Vaccines/adverse effects , COVID-19 Vaccines/immunology , COVID-19 Vaccines/administration & dosage , COVID-19/prevention & control , COVID-19/immunology , Female , Male , Child, Preschool , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , SARS-CoV-2/immunology , Vaccines, Subunit/immunology , Vaccines, Subunit/adverse effects , Vaccines, Subunit/administration & dosage , Vaccine Efficacy , Immunogenicity, Vaccine , Young Adult
2.
Clin Cancer Res ; 30(18): 4044-4054, 2024 Sep 13.
Article in English | MEDLINE | ID: mdl-39028916

ABSTRACT

PURPOSE: A multicenter, randomized, open-label, phase II study (HERIZON; NCT02795988) was conducted to evaluate the clinical and immunologic efficacy of HER-Vaxx (IMU-131), a B-cell, peptide-based vaccine targeting HER2 overexpressed in 6% to 30% of gastroesophageal adenocarcinomas (GEA). PATIENTS AND METHODS: Patients (n = 36) with GEA were treated with standard-of-care chemotherapy (n = 17) or HER-Vaxx plus chemotherapy (n = 19), using the recommended phase 2 dose for the vaccine. Overall survival (OS; primary endpoint), safety, progression-free survival (PFS), clinical response (secondary endpoints), and vaccine-induced HER2-specific antibody levels in serum and correlation with tumor response rates (exploratory endpoints) were investigated. RESULTS: A 40% OS benefit [HR, 0.60; median OS, 13.9 months; 80% confidence interval (CI), 7.52-14.32] for patients treated with HER-Vaxx plus chemotherapy compared with OS of 8.31 months (80% CI, 6.01-9.59) in patients that received chemotherapy alone. A 20% PFS difference was obtained for the vaccination arm (HR, 0.80; 80% CI, 0.47, 1.38). No additional toxicity due to HER-Vaxx was observed. The vaccine-induced high levels of HER2-specific total IgG and IgG1 antibodies (P < 0.001 vs. controls) that significantly correlated with tumor reduction (IgG, P = 0.001; IgG1, P = 0.016), had a significant capacity in inhibiting phosphorylation of the intracellular HER2-signaling pathways, mediated antibody-dependent cellular cytotoxicity, and decreased immunosuppressive FOXP3+ regulatory T cells. CONCLUSIONS: HER-Vaxx plus standard chemotherapy exhibits an excellent safety profile and improves OS. Furthermore, vaccine-induced immune response was significantly associated with reduced tumor size compared with standard-of-care chemotherapy. The presented vaccination approach may substitute for treatment with trastuzumab, upon unavailability or toxicity, based on further evidence of equivalent treatment efficacy.


Subject(s)
Cancer Vaccines , Receptor, ErbB-2 , Stomach Neoplasms , Humans , Receptor, ErbB-2/immunology , Receptor, ErbB-2/metabolism , Female , Middle Aged , Cancer Vaccines/administration & dosage , Cancer Vaccines/adverse effects , Cancer Vaccines/immunology , Cancer Vaccines/therapeutic use , Male , Aged , Stomach Neoplasms/drug therapy , Stomach Neoplasms/immunology , Stomach Neoplasms/pathology , Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Vaccines, Subunit/administration & dosage , Vaccines, Subunit/adverse effects , Vaccines, Subunit/therapeutic use , Vaccines, Subunit/immunology , Treatment Outcome , Neoplasm Staging , Aged, 80 and over
3.
Gynecol Oncol ; 189: 90-97, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39068739

ABSTRACT

OBJECTIVE: Folate receptor alpha (FRα) is overexpressed on >90% of high-grade epithelial ovarian cancers (EOC). Targeting FRα with antibody-drug conjugates has proven utility in the platinum-resistant setting. It is also a potential therapeutic target for immuno-oncologic agents, such as peptide vaccines that work primarily via adaptive and humoral immunity. We tested the hypothesis that FRα peptide immunization could improve outcomes in patients with EOC following response to platinum-based therapy. METHODS: We conducted a randomized, double-blind, multicenter, phase II study to evaluate the safety and efficacy of TPIV200 (a multi-epitope FRα peptide vaccine admixed with GM-CSF) versus GM-CSF alone in 120 women who did not have disease progression after at least 4 cycles of first-line platinum-based therapy. Patients were vaccinated intradermally once every 4 weeks up to 6 times, followed by a boosting period of 6 vaccinations at 12-week intervals. Primary endpoints included safety, tolerability, and progression free survival (PFS). RESULTS: At study termination with a median follow-up of 15.2 months (range 1.2-28.4 months), 68 of 119 intention-to-treat patients had disease progression (55% in TPIV200 + GM-CSF arm and 59% in GM-CSF alone arm). The median PFS was 11.1 months (95% CI 8.3-16.6 months) with no significant difference between the treatment groups (10.9 months with TPIV200 + GM-CSF versus 11.1 months with GM-CSF, HR, 0.85; upper 90% CI 1.17]. No patient experienced a ≥ grade 3 drug-related adverse event. CONCLUSION: TPIV200 was well tolerated but was not associated with improved PFS. Additional studies are required to uncover potential synergies using multiepitope vaccines targeting FRα. Trial Registration NLM/NCBI Registry, NCT02978222, https://clinicaltrials.gov/search?term=NCT02978222.


Subject(s)
Cancer Vaccines , Carcinoma, Ovarian Epithelial , Folate Receptor 1 , Granulocyte-Macrophage Colony-Stimulating Factor , Ovarian Neoplasms , Humans , Female , Folate Receptor 1/immunology , Middle Aged , Cancer Vaccines/administration & dosage , Cancer Vaccines/adverse effects , Cancer Vaccines/immunology , Cancer Vaccines/therapeutic use , Ovarian Neoplasms/immunology , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/therapy , Aged , Carcinoma, Ovarian Epithelial/immunology , Carcinoma, Ovarian Epithelial/drug therapy , Carcinoma, Ovarian Epithelial/therapy , Double-Blind Method , Adult , Granulocyte-Macrophage Colony-Stimulating Factor/administration & dosage , Granulocyte-Macrophage Colony-Stimulating Factor/immunology , Granulocyte-Macrophage Colony-Stimulating Factor/adverse effects , Granulocyte-Macrophage Colony-Stimulating Factor/therapeutic use , Vaccines, Subunit/administration & dosage , Vaccines, Subunit/immunology , Vaccines, Subunit/adverse effects , Progression-Free Survival , Aged, 80 and over
4.
Expert Rev Vaccines ; 23(1): 498-509, 2024.
Article in English | MEDLINE | ID: mdl-38695310

ABSTRACT

BACKGROUND: Vaccination remains the cornerstone of defense against COVID-19 globally. This study aims to assess the safety and immunogenicity profile of innovative vaccines LYB001. RESEARCH DESIGN AND METHODS: This was a randomized, double-blind, parallel-controlled trial, in 100 healthy Chinese adults (21 to 72 years old). Three doses of 30 or 60 µg of SARS-CoV-2 RBD-based VLP vaccine (LYB001), or the SARS-CoV-2 RBD-based protein subunit vaccine (ZF2001, control group) were administered with a 28-day interval. Differences in the incidence of adverse events (AEs) and indicators of humoral and cellular immunity among the different groups were measured. RESULTS: No severe adverse events were confirmed to be vaccine-related, and there was no significant difference in the rate of adverse events between the LYB001 and control group or the age subgroups (p > 0.05). The LYB001 groups had significantly higher or comparable levels of seroconversion rates, neutralization antibody, S protein-binding antibody, and cellular immunity after whole vaccination than the control group. CONCLUSIONS: Our findings support that LYB001 developed on the VLP platform is safe and well tolerated with favorable immunogenicity for fundamental vaccination in healthy adults. Therefore, further larger-scale clinical studies are warranted. TRIAL REGISTRATION: This trial was registered with ClinicalTrials.gov (NCT05552573).


Subject(s)
Antibodies, Neutralizing , Antibodies, Viral , COVID-19 Vaccines , COVID-19 , SARS-CoV-2 , Humans , Adult , Middle Aged , Double-Blind Method , COVID-19 Vaccines/immunology , COVID-19 Vaccines/adverse effects , COVID-19 Vaccines/administration & dosage , Male , Female , Antibodies, Viral/blood , Aged , Young Adult , Antibodies, Neutralizing/blood , SARS-CoV-2/immunology , COVID-19/prevention & control , COVID-19/immunology , Immunogenicity, Vaccine , Vaccines, Virus-Like Particle/immunology , Vaccines, Virus-Like Particle/adverse effects , Vaccines, Virus-Like Particle/administration & dosage , Immunity, Cellular , China , Immunity, Humoral , Spike Glycoprotein, Coronavirus/immunology , Vaccination/methods , Vaccines, Subunit/immunology , Vaccines, Subunit/adverse effects , Vaccines, Subunit/administration & dosage , East Asian People
5.
Lancet Rheumatol ; 6(6): e352-e360, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38710192

ABSTRACT

BACKGROUND: The adjuvanted herpes zoster subunit vaccine has shown good efficacy and safety in the general population. However, its effectiveness has not been comprehensively assessed in patients with systemic lupus erythematosus (SLE). This study aimed to evaluate the immunogenicity and safety of the adjuvanted herpes zoster subunit vaccine in patients with SLE. METHODS: This single-centre, randomised, double-blind, placebo-controlled, trial was done at the rheumatology outpatient clinic at Seoul National University Hospital, South Korea. Patients (aged ≥19 years) with clinically stable SLE and previous exposure (≥4 weeks) to immunosuppressive drugs were randomly assigned (4:1) via a central interactive web response system to receive herpes zoster subunit vaccine or placebo (0·5 mL intramuscular injection) at weeks 0 and 8. Investigators and participants were masked to intervention and group assignment. Anti-glycoprotein E antibody titres and glycoprotein E-specific cell-mediated vaccine responses were evaluated at baseline and at week 8 after the first dose, and at week 4, week 26, and week 52 after the second dose using enzyme-linked immunosorbent assay and flow cytometry, respectively. Reactogenicity, SLE disease activity, including Systemic Lupus Erythematosus Disease Activity Index 2000 and British Isles Lupus Assessment Group-flare rate, were examined. The primary outcome was the proportion of patients with a positive humoral vaccine response 4 weeks after the second dose. The primary and safety analyses were done in a modified intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT06001606. FINDINGS: Between June 14, and July 19, 2023, 65 patients with SLE were enrolled, of whom 52 were randomly assigned to the herpes zoster subunit vaccine and 13 to placebo. 49 patients in the vaccine group and 11 patients in the placebo group were included in the modified intention-to-treat population. 56 (93%) of 60 patients were women and four (7%) were men. Mean age was 48·7 years (SD 11·4). The proportion of participants with a humoral vaccine response at 4 weeks after the second dose was significantly higher in the vaccine group (48 [98%] of 49 participants) than the placebo group (none [0%] of 11 patients; p<0·0001). More patients in the vaccine group than placebo group reported injection site reactions (42 patients vs two patients), fever (ten vs none), and fatigue (26 vs two). There were no differences in Systemic Lupus Erythematosus Disease Activity Index 2000 and British Isles Lupus Assessment Group-flare rates between the groups. There were no treatment-related deaths. INTERPRETATION: The herpes zoster subunit vaccine induces humoral and cellular immunity against herpes zoster with a good safety profile in patients with SLE. A larger study is warranted to assess the efficacy of vaccines to prevent herpes zoster in patients with SLE. FUNDING: Ministry of Science and ICT, The Government of the Republic of Korea.


Subject(s)
Herpes Zoster Vaccine , Lupus Erythematosus, Systemic , Vaccines, Subunit , Humans , Lupus Erythematosus, Systemic/immunology , Female , Double-Blind Method , Male , Herpes Zoster Vaccine/immunology , Herpes Zoster Vaccine/administration & dosage , Herpes Zoster Vaccine/adverse effects , Republic of Korea/epidemiology , Adult , Middle Aged , Vaccines, Subunit/immunology , Vaccines, Subunit/administration & dosage , Vaccines, Subunit/adverse effects , Vaccines, Subunit/therapeutic use , Herpes Zoster/prevention & control , Herpes Zoster/immunology , Adjuvants, Immunologic/administration & dosage , Adjuvants, Immunologic/adverse effects , Immunogenicity, Vaccine , Antibodies, Viral/blood
6.
Vaccine ; 42(13): 3172-3179, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38616438

ABSTRACT

BACKGROUND: Bivalent RSV prefusion F subunit vaccine (RSVpreF), comprised of equal quantities of stabilized prefusion F antigens from the major circulating subgroups (RSV A, RSV B), is licensed for prevention of RSV-associated lower respiratory tract illness (LRTI) in older adults and for maternal vaccination for prevention of RSV-associated LRTI in infants. To support licensure and large-scale manufacturing, this lot consistency study was conducted to demonstrate equivalence in immunogenicity across 3 RSVpreF lots. METHODS: This phase 3, multicenter, parallel-group, placebo-controlled, randomized (1:1:1:1), double-blind study evaluated immunogenicity, safety, and tolerability of RSVpreF in healthy 18-49-year-old adults. Participants received a single 120-µg injection of 1 of 3RSVpreF lots or placebo. Geometric mean ratio (GMR) of RSV serum 50 % neutralizing geometric mean titers obtained 1 month after vaccination were compared between each vaccine lot for RSV A and RSV B, separately. Equivalence between lots was defined using a 1.5-fold criterion (GMR 95 % CIs for every lot pair within the 0.667-1.5 interval). Safety and tolerability were assessed. RESULTS: Of 992participants vaccinated, 948 were included in the evaluable immunogenicity population. All 3 RSVpreF lots elicited strong immune responses, meeting the 1.5-fold equivalence criterion for all between-lot comparisons for both RSV A and RSV B. Across the 3 lots, RSV A and RSV B 50 % neutralizing geometric mean titers substantially increased from baseline (RSV A, 1671-1795; RSV B 1358-1429) to 1 month after RSVpreF vaccination (RSV A, 24,131-25,238; RSV B, 19,238-21,702), corresponding to ≥14-fold increases in 50 % neutralizing titers for both RSV A and RSV B from before to 1 month after vaccination. Single doses of RSVpreF were safe and well tolerated, with similar safety profiles across the 3 RSVpreF lots. CONCLUSIONS: These findings support the reproducibility of RSVpreF vaccine manufacturing with similar safety and reactogenicity profiles (NCT05096208).


Subject(s)
Antibodies, Viral , Immunogenicity, Vaccine , Respiratory Syncytial Virus Infections , Respiratory Syncytial Virus Vaccines , Respiratory Syncytial Virus, Human , Humans , Respiratory Syncytial Virus Vaccines/immunology , Respiratory Syncytial Virus Vaccines/administration & dosage , Respiratory Syncytial Virus Vaccines/adverse effects , Female , Male , Adult , Double-Blind Method , Young Adult , Adolescent , Antibodies, Viral/blood , Middle Aged , Respiratory Syncytial Virus Infections/prevention & control , Respiratory Syncytial Virus Infections/immunology , Respiratory Syncytial Virus, Human/immunology , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Vaccines, Subunit/immunology , Vaccines, Subunit/administration & dosage , Vaccines, Subunit/adverse effects , Healthy Volunteers , Vaccination/methods , Viral Fusion Proteins/immunology
7.
Vaccine ; 42(5): 1051-1064, 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-37816655

ABSTRACT

SARS-CoV-2, severe acute respiratory syndrome coronavirus-2, causes coronavirus disease- 2019 (COVID-19). Mostly, COVID-19 causes respiratory symptoms that can resemble those of a cold, the flu, or pneumonia. COVID-19 may harm more than just lungs and respiratory systems. It may also have an impact on other parts of the body and debilitating effects on humans, necessitating the development of vaccines at an unprecedented rate in order to protect humans from infections. In response to SARS-CoV-2 infection, mRNA, viral vector-based carrier and inactivated virus-based vaccines, as well as subunit vaccines, have recently been developed. We developed Relcovax®, a dual antigen (Receptor binding domain (RBD) and Nucleocapsid (N) proteins) subunit protein vaccine candidate. Preliminary mouse preclinical studies revealed that Relcovax® stimulates cell-mediated immunity and provides broader protection against two SARS-CoV-2 variants, including the delta strain. Before conducting human studies, detailed preclinical safety assessments are required, so Relcovax® was tested for safety, and immunogenicity in 28-day repeated dose toxicity studies in rats and rabbits. In the toxicity studies, there were no mortality or morbidity, abnormal clinical signs, abnormalities in a battery of neurobehavioral observations, abnormalities in detailed clinical and ophthalmological examinations, or changes in body weights or feed consumption. In any of the studies, no abnormal changes in organ weights, haematology, clinical chemistry, urinalysis parameters, or pathological findings were observed. Immunogenicity tests on rats and rabbits revealed 100 % seroconversion. Relcovax® was therefore found to be safe in animals, with a No Observed Adverse Effect Level (NOAEL) of 20 µg/protein in rats and rabbits. In efficacy studies, Relcovax® immunised hamsters demonstrated dose-dependent protection against SARS-CoV-2 infection, with a high dose (20 µg/protein) being the most protective, while in cynomolgus macaque monkey study, lowest dose 5 µg/protein had the highest efficacy. In conclusion, Relcovax® was found to be safe, immunogenic, and efficacious in in vivo studies.


Subject(s)
COVID-19 , Vaccines, Subunit , Animals , Cricetinae , Humans , Mice , Rabbits , Rats , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , Immunogenicity, Vaccine , Nucleocapsid , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Vaccines, Subunit/adverse effects , Viral Vaccines
8.
Adv Rheumatol ; 63(1): 54, 2023 11 01.
Article in English | MEDLINE | ID: mdl-37915078

ABSTRACT

OBJECTIVE: This study aimed to analyze the safety and efficacy of COVID-19 vaccines among patients with chronic immune-mediated inflammatory disease (IMID) in China. METHODS: Participants who were diagnosed with a chronic IMID were eligible for inclusion in this study. Age- and sex-matched healthy vaccinated individuals were set as the control group. All participants received two doses of the inactivated CoronaVac vaccine or three doses of the recombinant protein subunit vaccine ZF2001. Adverse events, IMID activity after vaccination, and the rate of COVID-19 in the two groups were compared. RESULTS: There were 158 patients in the IMID group, with an average age of 40 ± 14 years old, and 98 female subjects. In the IMID group, 123 patients received the inactivated CoronaVac vaccine, and 35 patients received the recombinant protein subunit vaccine ZF2001. There were 153 individuals in the control group, including 122 who received the CoronaVac vaccine and 31 who received the recombinant protein subunit vaccine ZF2001. The frequency of vaccine-related adverse events in the IMID group was less than that in the control group, all of which were mild local effects, and no serious events occurred. Of note, no disease flares occurred in the IMID group. No participants in either group subsequently got COVID-19, so the incidence rate was 0% in both groups. CONCLUSION: COVID-19 vaccination was found to be safe for IMID subjects, any adverse events were mild, and vaccination did not increase the risk of disease activity. Meanwhile, vaccination could effectively reduce the incidence of COVID-19 in IMID patients. In the future, studies with a larger sample size and a longer duration are needed.


Subject(s)
COVID-19 Vaccines , COVID-19 , Adult , Female , Humans , Middle Aged , Chronic Disease , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Recombinant Proteins/adverse effects , Vaccination/adverse effects , Vaccines, Subunit/adverse effects , Male
9.
Aten Primaria ; 55(10): 102710, 2023 10.
Article in Spanish | MEDLINE | ID: mdl-37573820

ABSTRACT

OBJECTIVE: To review the latest published evidence on the vaccine used in our country against the herpes zoster virus, breaking down the results according to the efficacy, efficiency, effectiveness and safety of the vaccine. Include the current recommendations for vaccination. DESIGN: Secondary review. Descriptive qualitative review. Review using the search term "herpes zoster vaccine" and "Adjuvanted recombinant Herpes Zoster subunit vaccine". Retrospective observational study. DATA SOURCES: Embase, Medline and Google Scholar. Selection of studies Search criterion with the terms "Shingrix vaccine" and "Adjuvanted Herpes Zoster Subunit Vaccine". Search period 2013-2023. Studies classified as clinical trials or randomized clinical trials were selected. 21 published studies were evaluated. There were no exclusions. RESULTS: The evaluated studies were found to be coherent and in all of them efficacy in adult individuals in preventing viral reactivation and in preventing complications was higher than 80%. The effectiveness of the vaccine after two doses was also higher than 80%. Cost-effectiveness studies were always favourable in adults, immunodepressed patients and individuals with chronic pathology. The safety of the vaccine was evaluated in the pivotal studies and in the post-commercialization studies that were undertaken (although there were few of the latter due to the short period of time studied). The safety profile of the vaccine is very high and in the case of severe adverse effects, their frequency was similar to that of a placebo. CONCLUSIONS: We have a safe and effective vaccine against the herpes zoster virus that allows us to protect the most vulnerable population groups against this virus.


Subject(s)
Herpes Zoster Vaccine , Herpes Zoster , Adult , Humans , Herpesvirus 3, Human , Herpes Zoster/prevention & control , Vaccination , Vaccines, Subunit/adverse effects
10.
Cancer Prev Res (Phila) ; 16(6): 333-341, 2023 06 01.
Article in English | MEDLINE | ID: mdl-37259799

ABSTRACT

NeuVax is a vaccine comprised of the HER2-derived MHC class I peptide E75 (nelipepimut-S, NPS) combined with GM-CSF. We completed a randomized trial of preoperative vaccination with NeuVax versus GM-CSF alone in patients with ductal carcinoma in situ (DCIS). The primary objective was to evaluate for NPS-specific cytotoxic T lymphocyte (CTL) responses. Patients with human leukocyte antigen (HLA)-A2-positive DCIS were enrolled and randomized 2:1 to NeuVax versus GM-CSF alone and received two inoculations prior to surgery. The number of NPS-specific CTL was measured pre-vaccination, at surgery, and 1 and 3 to 6 months post-operation by dextramer assay. Differences in CTL responses between groups and between pre-vaccination and 1-month post-operation were analyzed using a two-sample t test or Wilcoxon rank sum test. The incidence and severity of adverse events were compared between groups. Overall, 45 patients were registered; 20 patients were HLA-A2 negative, 7 declined participation, 1 withdrew, and 4 failed screening for other reasons. The remaining 13 were randomized to NeuVax (n = 9) or GM-CSF alone (n = 4). Vaccination was well-tolerated with similar treatment-related toxicity between groups with the majority (>89%) of adverse events being grade 1. The percentage of NPS-specific CTLs increased in both arms between baseline (pre-vaccination) and 1-month post-operation. The increase was numerically greater in the NPS+GM-CSF arm, but the difference was not statistically significant. NPS+GM-CSF is safe and well-tolerated when given preoperatively to patients with DCIS. In patients with HLA-A2-positive DCIS, two inoculations with NPS+GM-CSF can induce in vivo immunity and a continued antigen-specific T-cell response 1-month postsurgery. PREVENTION RELEVANCE: This trial showed that vaccination of patients with HLA-A2-positive DCIS with NeuVax in the preoperative setting can induce a sustained antigen-specific T-cell response. This provides proof of principle that vaccination in the preoperative or adjuvant setting may stimulate an adaptive immune response that could potentially prevent disease recurrence.


Subject(s)
Cancer Vaccines , Carcinoma, Intraductal, Noninfiltrating , Humans , Female , Granulocyte-Macrophage Colony-Stimulating Factor , Carcinoma, Intraductal, Noninfiltrating/surgery , HLA-A2 Antigen , Neoplasm Recurrence, Local/pathology , Peptide Fragments , Vaccines, Subunit/adverse effects , Cancer Vaccines/adverse effects
11.
Kurume Med J ; 68(2): 157-163, 2023 Jul 03.
Article in English | MEDLINE | ID: mdl-37183020

ABSTRACT

This case series aimed to evaluate the peptide-specific immunoglobulin G (IgG) response, clinical effectiveness, and the safety of a personalized peptide vaccine (PPV) in four children with refractory solid cancer. Although the pre-vaccination IgG responses were suppressed, IgG levels against the vaccinated peptides after 12 vaccinations were increased in all three cases who received at least 12 vaccinations. Vaccination-related adverse effects were grade 1 injection-site local skin lesions. One patient, whose diagnosis was relapsed rhabdomyosarcoma, remains in sustained remission after 37 months. Although the pre-vaccination immune response in this patient was low, IgG levels against 2 of the 4 peptide vaccines were increased after the sixth vaccination, followed by a strong increase at the eighteenth vaccination against all 4 peptides, with a >100-fold increase vs. 2 peptides. The remaining three patients exhibited progressive disease and eventually died of their original cancer. The results of the current case series suggest that in cases of childhood solid tumors, when the tumor is controlled at the time of entry PPV may have some consolidation effect. Therefore, PPV could be a new immunotherapy modality for refractory childhood solid tumors.


Subject(s)
Soft Tissue Neoplasms , Vaccines, Subunit , Child , Humans , Immunoglobulin G , Peptides , Soft Tissue Neoplasms/chemically induced , Soft Tissue Neoplasms/drug therapy , Treatment Outcome , Vaccines, Subunit/adverse effects
12.
Nat Commun ; 14(1): 1138, 2023 03 06.
Article in English | MEDLINE | ID: mdl-36878897

ABSTRACT

Adjuvant-containing subunit vaccines represent a promising approach for protection against tuberculosis (TB), but current candidates require refrigerated storage. Here we present results from a randomized, double-blinded Phase 1 clinical trial (NCT03722472) evaluating the safety, tolerability, and immunogenicity of a thermostable lyophilized single-vial presentation of the ID93 + GLA-SE vaccine candidate compared to the non-thermostable two-vial vaccine presentation in healthy adults. Participants were monitored for primary, secondary, and exploratory endpoints following intramuscular administration of two vaccine doses 56 days apart. Primary endpoints included local and systemic reactogenicity and adverse events. Secondary endpoints included antigen-specific antibody (IgG) and cellular immune responses (cytokine-producing peripheral blood mononuclear cells and T cells). Both vaccine presentations are safe and well tolerated and elicit robust antigen-specific serum antibody and Th1-type cellular immune responses. Compared to the non-thermostable presentation, the thermostable vaccine formulation generates greater serum antibody responses (p < 0.05) and more antibody-secreting cells (p < 0.05). In this work, we show the thermostable ID93 + GLA-SE vaccine candidate is safe and immunogenic in healthy adults.


Subject(s)
Immunogenicity, Vaccine , Tuberculosis Vaccines , Vaccines, Subunit , Adult , Humans , Adjuvants, Immunologic/adverse effects , Adjuvants, Immunologic/pharmacology , Adjuvants, Immunologic/therapeutic use , Antibodies/immunology , Antibody-Producing Cells/immunology , Leukocytes, Mononuclear/immunology , Tuberculosis Vaccines/adverse effects , Tuberculosis Vaccines/immunology , Tuberculosis Vaccines/pharmacology , Tuberculosis Vaccines/therapeutic use , Immunogenicity, Vaccine/immunology , Treatment Outcome , Healthy Volunteers , Temperature , Vaccines, Subunit/administration & dosage , Vaccines, Subunit/adverse effects , Vaccines, Subunit/immunology , Vaccines, Subunit/pharmacology , Vaccines, Subunit/therapeutic use , Double-Blind Method
13.
Vaccine ; 41(13): 2253-2260, 2023 03 24.
Article in English | MEDLINE | ID: mdl-36868877

ABSTRACT

BACKGROUND: We evaluated the safety of SCB-2019, a protein subunit vaccine candidate containing a recombinant SARS-CoV-2 spike (S) trimer fusion protein, combined with CpG-1018/alum adjuvants. METHODS: This ongoing phase 2/3, double-blind, placebo-controlled, randomized trial is being conducted in Belgium, Brazil, Colombia, the Philippines, and South Africa in participants ≥ 12 years of age. Participants were randomly assigned to receive 2 doses of SCB-2019 or placebo administered intramuscularly 21 days apart. Here, we present the safety results of SCB-2019 over the 6-month period following 2-dose primary vaccination series in all adult participants (≥18 years of age). RESULTS: A total of 30,137 adult participants received at least one dose of study vaccine (n = 15,070) or placebo (n = 15,067) between 24 March 2021 and 01 December 2021. Unsolicited adverse events, medically-attended adverse events, adverse events of special interest, and serious adverse events were reported in similar frequencies in both study arms over the 6-month follow-up period. Vaccine-related SAEs were reported by 4 of 15,070 SCB-2019 recipients (hypersensitivity reactions in two participants, Bell's palsy, and spontaneous abortion) and 2 of 15,067 placebo recipients (COVID-19, pneumonia, and acute respiratory distress syndrome in one participant and spontaneous abortion in the other one). No signs of vaccine-associated enhanced disease were observed. CONCLUSIONS: SCB-2019 administered as a 2-dose series has an acceptable safety profile. No safety concerns were identified during the 6-month follow-up after the primary vaccination. CLINICAL TRIALS REGISTRATION: NCT04672395; EudraCT: 2020-004272-17.


Subject(s)
Abortion, Spontaneous , COVID-19 , Pregnancy Complications, Infectious , Female , Pregnancy , Adult , Humans , COVID-19/prevention & control , SARS-CoV-2 , Protein Subunits , Abortion, Spontaneous/chemically induced , Follow-Up Studies , Vaccines, Subunit/adverse effects , Adjuvants, Immunologic/adverse effects , Double-Blind Method , Immunogenicity, Vaccine , Antibodies, Viral , Pregnancy Complications, Infectious/chemically induced
14.
Int J Mol Sci ; 24(3)2023 Feb 01.
Article in English | MEDLINE | ID: mdl-36769094

ABSTRACT

Shiga toxin-producing Escherichia coli (STEC) is a zoonotic pathogen that causes gastroenteritis and Hemolytic Uremic Syndrome. Cattle are the main animal reservoir, excreting the bacteria in their feces and contaminating the environment. In addition, meat can be contaminated by releasing the intestinal content during slaughtering. Here, we evaluated the safety and immunogenicity of a vaccine candidate against STEC that was formulated with two chimeric proteins (Chi1 and Chi2), which contain epitopes of the OmpT, Cah and Hes proteins. Thirty pregnant cows in their third trimester of gestation were included and distributed into six groups (n = 5 per group): four groups were administered intramuscularly with three doses of the formulation containing 40 µg or 100 µg of each protein plus the Quil-A or Montanide™ Gel adjuvants, while two control groups were administered with placebos. No local or systemic adverse effects were observed during the study, and hematological parameters and values of blood biochemical indicators were similar among all groups. Furthermore, all vaccine formulations triggered systemic anti-Chi1/Chi2 IgG antibody levels that were significantly higher than the control groups. However, specific IgA levels were generally low and without significant differences among groups. Notably, anti-Chi1/Chi2 IgG antibody levels in the serum of newborn calves fed with colostrum from their immunized dams were significantly higher compared to newborn calves fed with colostrum from control cows, suggesting a passive immunization through colostrum. These results demonstrate that this vaccine is safe and immunogenic when applied to pregnant cows during the third trimester of gestation.


Subject(s)
Escherichia coli Infections , Hemolytic-Uremic Syndrome , Shiga-Toxigenic Escherichia coli , Vaccines, Subunit , Animals , Cattle , Female , Pregnancy , Escherichia coli Infections/prevention & control , Escherichia coli Infections/veterinary , Immunization, Passive , Immunoglobulin G , Vaccines, Subunit/adverse effects
15.
J Clin Oncol ; 41(2): 373-384, 2023 01 10.
Article in English | MEDLINE | ID: mdl-36070539

ABSTRACT

PURPOSE: Universal cancer peptide-based vaccine (UCPVax) is a therapeutic vaccine composed of two highly selected helper peptides to induce CD4+ T helper-1 response directed against telomerase. This phase Ib/IIa trial was designed to test the safety, immunogenicity, and efficacy of a three-dose schedule in patients with metastatic non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with refractory NSCLC were assigned to receive three vaccination doses of UCPVax (0.25 mg, 0.5 mg, and 1 mg) using a Bayesian-based phase Ib followed by phase IIa de-escalating design. The primary end points were dose-limiting toxicity and immune response after three first doses of vaccine. Secondary end points were overall survival (OS) and progression-free survival at 1 year. RESULTS: A total of 59 patients received UCPVax; 95% had three prior lines of systemic therapy. No dose-limiting toxicity was observed in 15 patients treated in phase Ib. The maximum tolerated dose was 1 mg. Fifty-one patients were eligible for phase IIa. The third and sixth dose of UCPVax induced specific CD4+ T helper 1 response in 56% and 87.2% of patients, respectively, with no difference between three dose levels. Twenty-one (39%) patients achieved disease control (stable disease, n = 20; complete response, n = 1). The 1-year OS was 34.1% (95% CI, 23.1 to 50.4), and the median OS was 9.7 months, with no significant difference between dose levels. The 1-year progression-free survival and the median OS were 17.2% (95% CI, 7.8 to 38.3) and 11.6 months (95% CI, 9.7 to 16.7) in immune responders (P = .015) and 4.5% (95% CI, 0.7 to 30.8) and 5.6 months (95% CI, 2.5 to 10) in nonresponders (P = .005), respectively. CONCLUSION: UCPVax was highly immunogenic and safe and provide interesting 1-year OS rate in heavily pretreated advanced NSCLC.


Subject(s)
Cancer Vaccines , Carcinoma, Non-Small-Cell Lung , Immunogenicity, Vaccine , Lung Neoplasms , Humans , Bayes Theorem , Cancer Vaccines/adverse effects , Cancer Vaccines/immunology , Cancer Vaccines/therapeutic use , Carcinoma, Non-Small-Cell Lung/therapy , Lung Neoplasms/therapy , Vaccines, Subunit/adverse effects , Vaccines, Subunit/immunology , Vaccines, Subunit/therapeutic use
16.
Expert Rev Vaccines ; 22(1): 35-53, 2023.
Article in English | MEDLINE | ID: mdl-36484136

ABSTRACT

INTRODUCTION: Vaccines prevent disease and disability; save lives and represent a good assessment of health interventions. Several systematic reviews on the efficacy and effectiveness of COVID-19 vaccines have been published, but the immunogenicity and safety of these vaccines should also be addressed. AREAS COVERED: This systemic investigation sought to explain the efficacy, immunogenicity, and safety of new vaccination technologies against SARS-CoV-2 in people over 18 years old. Original research studying the effectiveness on mRNA, protein subunit vaccines, and viral vector vaccines against SARS-CoV-2 in people over 18 years old was analyzed. Several databases (Web of Science, Scopus, MEDLINE and EMBASE) were searched between 2012 and November 2022 for English-language papers using text and MeSH terms related to SARS-CoV-2, mechanism, protein subunit vaccine, viral vector, and mRNA. The protocol was registered on PROSPERO, CRD42022341952. Study quality was assessed using the NICE methodology. We looked at a total of six original articles. All studies gathered and presented quantitative data. EXPERT OPINION: Our results suggest that new vaccinations could have more than 90% efficacy against SARS-CoV-2, regardless of the technology used. Furthermore, adverse reactions go from mild to moderate, and good immunogenicity can be observed for all vaccine types.


Subject(s)
COVID-19 , Viral Vaccines , Humans , Adolescent , Protein Subunits , COVID-19 Vaccines/adverse effects , SARS-CoV-2 , RNA, Messenger , COVID-19/prevention & control , Vaccines, Subunit/adverse effects , Antibodies, Viral , Immunogenicity, Vaccine
17.
Front Immunol ; 13: 1023023, 2022.
Article in English | MEDLINE | ID: mdl-36330525

ABSTRACT

Background: Arginase-1-producing cells inhibit T cell-mediated anti-tumor responses by reducing L-arginine levels in the tumor microenvironment. T cell-facilitated elimination of arginase-1-expressing cells could potentially restore L-arginine levels and improve anti-tumor responses. The activation of arginase-1-specific T cells may convert the immunosuppressive tumor microenvironment and induce or strengthen local Th1 inflammation. In the current clinical study, we examined the safety and immunogenicity of arginase-1-based peptide vaccination. Methods: In this clinical phase I trial, ten patients with treatment-refractory progressive solid tumors were treated. The patients received an arginase-1 peptide vaccine comprising three 20-mer peptides from the ARG1 immunological "hot spot" region in combination with the adjuvant Montanide ISA-51. The vaccines were administered subcutaneously every third week (maximum 16 vaccines). The primary endpoint was to evaluate safety assessed by Common Terminology Criteria for Adverse Events 4.0 and laboratory monitoring. Vaccine-specific immune responses were evaluated using enzyme-linked immune absorbent spot assays and intracellular cytokine staining on peripheral blood mononuclear cells. Clinical responses were evaluated using Response Evaluation Criteria in Solid Tumors 1.1. Results: The vaccination was feasible, and no vaccine-related grade 3-4 adverse events were registered. Nine (90%) of ten patients exhibited peptide-specific immune responses in peripheral blood mononuclear cells. Six (86%) of the seven evaluable patients developed a reactive T cell response against at least one of the ARG1 peptides during treatment. A phenotypic classification revealed that arginase-1 vaccine-specific T cells were both CD4+ T cells and CD8+ T cells. Two (20%) of ten patients obtained stable disease for respectively four- and seven months on vaccination treatment. Conclusion: The peptide vaccine against arginase-1 was safe. Nine (90%) of ten patients had measurable peptide-specific responses in the periphery blood, and two (20%) of ten patients attained stable disease on protocol treatment. Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT03689192, identifier NCT03689192.


Subject(s)
Cancer Vaccines , Neoplasms , Humans , Cancer Vaccines/adverse effects , Vaccines, Subunit/adverse effects , Arginase , Leukocytes, Mononuclear , Neoplasms/drug therapy , Peptides/therapeutic use , Arginine , Tumor Microenvironment
18.
Front Immunol ; 13: 1017590, 2022.
Article in English | MEDLINE | ID: mdl-36426361

ABSTRACT

Background: In response to SARS-CoV-2 mutations and waning antibody levels after two-dose inactivated vaccines, we assessed whether a third dose of recombinant protein subunit vaccine (ZF2001) boosts immune responses. Methods: An open-label single-center non-random trial was conducted on people aged 18 years and above at five sites in China. All participants received a two-dose inactivated vaccine (CoronaVac) as their prime doses within 3-9 months of the trial. Primary outcomes were safety and immunogenicity, primarily the geometric mean titers (GMTs) of neutralizing antibodies to live wildtype SARS-CoV-2. Results: A total of 480 participants (median age, 51; range 21-84 years) previously vaccinated with two-dose CoronaVac received a third booster dose of ZF2001 3-4, 5-6, or 7-9-months later. The overall incidence of adverse reactions within 30 days after vaccination was 5.83% (28/480). No serious adverse reactions were reported after the third dose of ZF2001. GMTs in the 3-4-, 5-6-, and 7-9-month groups before vaccination were 3.96, 4.60, and 3.78, respectively. On Day 14, GMTs increased to 33.06, 47.51, and 44.12, respectively. After the booster, GMTs showed no significant difference among the three prime-boost interval groups (all P>0.05). Additionally, GMTs in older adults were lower than those in younger adults on Day 14 for the three groups (P=0.0005, P<0.0001, and P<0.0001). Conclusion: Heterologous boosting with ZF2001 was safe and immunogenic, and prime-boost intervals did not affect the immune response. The immune response was weaker in older than younger adults.


Subject(s)
COVID-19 Vaccines , COVID-19 , Aged , Humans , Middle Aged , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Protein Subunits , SARS-CoV-2 , Vaccines, Inactivated/administration & dosage , Vaccines, Subunit/adverse effects , Vaccines, Synthetic/adverse effects , Young Adult , Adult , Aged, 80 and over
19.
F1000Res ; 11: 259, 2022.
Article in English | MEDLINE | ID: mdl-36176546

ABSTRACT

A systematic review of clinical trials conducted with a low-dose inactivated influenza vaccine adjuvanted by azoximer bromide (AZB, Polyoxidonium), was performed to compare vaccine reactogenicity against non-adjuvant vaccines. We also assessed whether lower amounts of antigen per viral strain in AZB-adjuvanted vaccines affected antibody responses. A robust search strategy identified scientific publications reporting 30 clinical trials, comprising data on 11,736 participants and 86 trial arms, for inclusion in the analysis. Local reaction rates (R lr) appeared to be lower in AZB-adjuvanted vaccine treatment arms versus comparator vaccine treatment arms. Post-vaccination geometric mean titres in those exposed to AZB-adjuvanted vaccine and comparator vaccine treatment arms were similar in both children and adults aged 18-60 years, implying an antigen-sparing effect by AZB. Meta­regression analysis based on a literature search of records or reports of clinical trials featuring AZB and the inactivated subunit of influenza published between 1998-2018 was conducted online in January 2019 and updated in August 2019. This search covered trials performed between 1993 and 2016 and suggested that AZB did not contribute to vaccine reactogenicity.


Subject(s)
Influenza Vaccines , Influenza, Human , Adult , Child , Humans , Influenza Vaccines/adverse effects , Influenza, Human/prevention & control , Antibodies, Viral , Polymers , Adjuvants, Immunologic/adverse effects , Vaccines, Inactivated/adverse effects , Vaccines, Subunit/adverse effects
20.
N Engl J Med ; 386(22): 2097-2111, 2022 06 02.
Article in English | MEDLINE | ID: mdl-35507481

ABSTRACT

BACKGROUND: The ZF2001 vaccine, which contains a dimeric form of the receptor-binding domain of severe acute respiratory syndrome coronavirus 2 and aluminum hydroxide as an adjuvant, was shown to be safe, with an acceptable side-effect profile, and immunogenic in adults in phase 1 and 2 clinical trials. METHODS: We conducted a randomized, double-blind, placebo-controlled, phase 3 trial to investigate the efficacy and confirm the safety of ZF2001. The trial was performed at 31 clinical centers across Uzbekistan, Indonesia, Pakistan, and Ecuador; an additional center in China was included in the safety analysis only. Adult participants (≥18 years of age) were randomly assigned in a 1:1 ratio to receive a total of three 25-µg doses (30 days apart) of ZF2001 or placebo. The primary end point was the occurrence of symptomatic coronavirus disease 2019 (Covid-19), as confirmed on polymerase-chain-reaction assay, at least 7 days after receipt of the third dose. A key secondary efficacy end point was the occurrence of severe-to-critical Covid-19 (including Covid-19-related death) at least 7 days after receipt of the third dose. RESULTS: Between December 12, 2020, and December 15, 2021, a total of 28,873 participants received at least one dose of ZF2001 or placebo and were included in the safety analysis; 25,193 participants who had completed the three-dose regimen, for whom there were approximately 6 months of follow-up data, were included in the updated primary efficacy analysis that was conducted at the second data cutoff date of December 15, 2021. In the updated analysis, primary end-point cases were reported in 158 of 12,625 participants in the ZF2001 group and in 580 of 12,568 participants in the placebo group, for a vaccine efficacy of 75.7% (95% confidence interval [CI], 71.0 to 79.8). Severe-to-critical Covid-19 occurred in 6 participants in the ZF2001 group and in 43 in the placebo group, for a vaccine efficacy of 87.6% (95% CI, 70.6 to 95.7); Covid-19-related death occurred in 2 and 12 participants, respectively, for a vaccine efficacy of 86.5% (95% CI, 38.9 to 98.5). The incidence of adverse events and serious adverse events was balanced in the two groups, and there were no vaccine-related deaths. Most adverse reactions (98.5%) were of grade 1 or 2. CONCLUSIONS: In a large cohort of adults, the ZF2001 vaccine was shown to be safe and effective against symptomatic and severe-to-critical Covid-19 for at least 6 months after full vaccination. (Funded by the National Science and Technology Major Project and others; ClinicalTrials.gov number, NCT04646590.).


Subject(s)
COVID-19 Vaccines , COVID-19 , Vaccines, Subunit , Adolescent , Adult , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , COVID-19 Vaccines/therapeutic use , Double-Blind Method , Humans , SARS-CoV-2 , Vaccination , Vaccines , Vaccines, Subunit/adverse effects , Vaccines, Subunit/therapeutic use , Young Adult
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