A first-time-in Human (FTIH), Phase I/II, Randomized, Multi-centric, Single-blind, Controlled Dose-escalation Study to Evaluate the Reactogenicity, Safety, Immunogenicity and Efficacy of GSK Biologicals' HBV Viral Vector Vaccines Given in a Prime-boost Schedule With Sequential or Co-administration of Adjuvanted Proteins Therapeutic Vaccine (GSK3528869A) in Chronic Hepatitis B Patients (18-65 Years Old) Well Controlled Under Nucleo(s)Tide Analogue (NA) Therapy
A First-Time-In-Human study on GSK's therapeutic vaccines to evaluate the reactogenicity, safety, immunogenicity and efficacy on reduction of serum HBV surface antigen in HBV suppressed subjects under nucleo(s)tide treatment.
Safety, tolerability, and immunogenicity of the Ebola Sudan chimpanzee adenovirus vector vaccine (cAd3-EBO S) in healthy Ugandan adults: a phase 1, open-label, dose-escalation clinical trial.
作者: Betty Mwesigwa ; Katherine V Houser ; Amelia R Hofstetter ; Ana M Ortega-Villa ; Prossy Naluyima ; Francis Kiweewa ; Immaculate Nakabuye ; Galina V Yamshchikov ; Charla Andrews ; Mark O'Callahan ; Larisa Strom ; Steven Schech ; Leigh Anne Eller ; Erica L Sondergaard ; Paul T Scott ; Mihret F Amare ; Kayvon Modjarrad ; Amir Wamala ; Allan Tindikahwa ; Ezra Musingye ; Jauhara Nanyondo ; Martin R Gaudinski ; Ingelise J Gordon ; LaSonji A Holman ; Jamie G Saunders ; Pamela J M Costner ; Floreliz H Mendoza ; Myra Happe ; Patricia Morgan ; Sarah H Plummer ; Somia P Hickman ; Sandra Vazquez ; Tamar Murray ; Jamilet Cordon ; Caitlyn N M Dulan ; Ruth Hunegnaw ; Manjula Basappa ; Marcelino Padilla ; Suprabhath R Gajjala ; Phillip A Swanson ; Bob C Lin ; Emily E Coates ; Jason G Gall ; Adrian B McDermott ; Richard A Koup ; John R Mascola ; Aurélie Ploquin ; Nancy J Sullivan ; Hannah Kibuuka ; Julie A Ake ; Julie E Ledgerwood ; RV 508 Study Team
Sudan Ebola virus can cause severe viral disease, with an average case fatality rate of 54%. A recent outbreak of Sudan Ebola virus in Uganda caused 55 deaths among 164 confirmed cases in the second half of 2022. Although vaccines and therapeutics specific for Zaire Ebola virus have been approved for use during outbreak situations, Sudan Ebola virus is an antigenically distinct virus with no approved vaccines available.
In this phase 1, open-label, dose-escalation trial we evaluated the safety, tolerability, and immunogenicity of a monovalent chimpanzee adenovirus 3 vaccine against Sudan Ebola virus (cAd3-EBO S) at Makerere University Walter Reed Project in Kampala, Uganda. Study participants were recruited from the Kampala metropolitan area using International Review Board-approved written and electronic media explaining the trial intervention. Healthy adults without previous receipt of Ebola, Marburg, or cAd3 vectored-vaccines were enrolled to receive cAd3-EBO S at either 1 × 1010 or 1 × 1011 particle units (PU) in a single intramuscular vaccination and were followed up for 48 weeks. Primary safety and tolerability endpoints were assessed in all vaccine recipients by reactogenicity for the first 7 days, adverse events for the first 28 days, and serious adverse events throughout the study. Secondary immunogenicity endpoints included evaluation of binding antibody and T-cell responses against the Sudan Ebola virus glycoprotein, and neutralising antibody responses against the cAd3 vector at 4 weeks after vaccination. This study is registered with ClinicalTrials.gov, NCT04041570, and is completed.
40 healthy adults were enrolled between July 22 and Oct 1, 2019, with 20 receiving 1 × 1010 PU and 20 receiving 1 × 1011 PU of cAd3-EBO S. 38 (95%) participants completed all follow-up visits. The cAd3-EBO S vaccine was well tolerated with no severe adverse events. The most common reactogenicity symptoms were pain or tenderness at the injection site (34 [85%] of 40), fatigue (29 [73%] of 40), and headache (26 [65%] of 40), and were mild to moderate in severity. Positive responses for glycoprotein-specific binding antibodies were induced by 2 weeks in 31 (78%) participants, increased to 34 (85%) participants by 4 weeks, and persisted to 48 weeks in 31 (82%) participants. Most participants developed glycoprotein-specific T-cell responses (20 [59%, 95% CI 41-75] of 34; six participants were removed from the T cell analysis after failing quality control parameters) by 4 weeks after vaccination, and neutralising titres against the cAd3 vector were also increased from baseline (90% inhibitory concentration of 47, 95% CI 30-73) to 4 weeks after vaccination (196, 125-308).
The cAd3-EBO S vaccine was safe at both doses, rapidly inducing immune responses in most participants after a single injection. The rapid onset and durability of the vaccine-induced antibodies make this vaccine a strong candidate for emergency deployment in Sudan Ebola virus outbreaks.
National Institutes of Health via interagency agreement with Walter Reed Army Institute of Research.
2023-07-12·Science translational medicine
Vaccination with Plasmodium vivax Duffy-binding protein inhibits parasite growth during controlled human malaria infection.
作者: Mimi M Hou ; Jordan R Barrett ; Yrene Themistocleous ; Thomas A Rawlinson ; Ababacar Diouf ; Francisco J Martinez ; Carolyn M Nielsen ; Amelia M Lias ; Lloyd D W King ; Nick J Edwards ; Nicola M Greenwood ; Lucy Kingham ; Ian D Poulton ; Baktash Khozoee ; Cyndi Goh ; Susanne H Hodgson ; Dylan J Mac Lochlainn ; Jo Salkeld ; Micheline Guillotte-Blisnick ; Christèle Huon ; Franziska Mohring ; Jenny M Reimer ; Virander S Chauhan ; Paushali Mukherjee ; Sumi Biswas ; Iona J Taylor ; Alison M Lawrie ; Jee-Sun Cho ; Fay L Nugent ; Carole A Long ; Robert W Moon ; Kazutoyo Miura ; Sarah E Silk ; Chetan E Chitnis ; Angela M Minassian ; Simon J Draper
There are no licensed vaccines against Plasmodium vivax. We conducted two phase 1/2a clinical trials to assess two vaccines targeting P. vivax Duffy-binding protein region II (PvDBPII). Recombinant viral vaccines using chimpanzee adenovirus 63 (ChAd63) and modified vaccinia virus Ankara (MVA) vectors as well as a protein and adjuvant formulation (PvDBPII/Matrix-M) were tested in both a standard and a delayed dosing regimen. Volunteers underwent controlled human malaria infection (CHMI) after their last vaccination, alongside unvaccinated controls. Efficacy was assessed by comparisons of parasite multiplication rates in the blood. PvDBPII/Matrix-M, given in a delayed dosing regimen, elicited the highest antibody responses and reduced the mean parasite multiplication rate after CHMI by 51% (n = 6) compared with unvaccinated controls (n = 13), whereas no other vaccine or regimen affected parasite growth. Both viral-vectored and protein vaccines were well tolerated and elicited expected, short-lived adverse events. Together, these results support further clinical evaluation of the PvDBPII/Matrix-M P. vivax vaccine.
2022-12-17·Fertility and sterility
The type of SARS-CoV-2 vaccine does not affect ovarian function in assisted reproduction cycle.
作者: Antonio Requena ; Vanessa Vergara ; Cristina González-Ravina ; Maria Eugenia Ruiz ; María Cruz
To assess if vaccination or the type of vaccination against SARS-CoV-2 affects ovarian function in an assisted reproduction treatment.
Retrospective and observational study.
University-affiliated private IVF.
510 patients who had received the complete vaccination schedule.
Pre-vaccine and post-vaccine treatment.
MAIN OUTCOME MEASURES:
Parameters for both reproductive outcomes and IVF results in patients vaccinated RESULTS: We included 510 patients, distributed as follows: 13.5% (n = 69) received a viral vector vaccine, either the adenovirus serotype 26 vector vaccine (Ad26.CoV2.S; Janssen; n = 31) or the chimpanzee adenovirus vector vaccine (ChAdOx; AstraZeneca; n = 38). The remaining 86.5% (n = 441) received an mRNA vaccine from either Pfizer-BioNTech (n = 336) or Moderna (n = 105). Sample size for the unexposed women was n = 1190. No differences were found in any of the evaluated parameters for both reproductive outcomes and IVF results in patients vaccinated with any adenovirus or mRNA vaccine. When we compared the post-vaccination results between the different types of vaccines and the unexposed group, similar results were obtained in the days of stimulation or the doses of FSH administered. Finally, the numbers of oocytes were as follows: Johnson & Johnson (9.2 ± 2.6), AstraZeneca (7.7 ± 1.2), Moderna (11.3 ± 1.8), Pfizer (12.6 ± 1.0), and the unvaccinated group (10.2 ± 1.5), P = 0.057.
These early results suggest no measurable detrimental effect on reproductive outcomes, regardless of the type of vaccine received.