Pooled safety evaluation for a new single-shot live-attenuated chikungunya vaccine†.

Background: Chikungunya disease, caused by chikungunya virus (CHIKV), is associated with substantial morbidity, including debilitating CHIKV-related arthralgia.

Methods: Three clinical trials of a CHIKV vaccine (VLA1553, IXCHIQ®) were conducted in the USA: a Phase 1 dose-finding trial, a pivotal Phase 3 trial and a Phase 3 lot-to-lot consistency trial. Participants were healthy adults (≥18 years) and received a single intramuscular dose of VLA1553 (3520 participants) or placebo (1033 participants).

From bench to clinic: the development of VLA1553/IXCHIQ, a live-attenuated chikungunya vaccine.

Background: Over the past 20 years, over 5 million cases of chikungunya, a mosquito-transmitted viral disease, have been reported in over 110 countries. Until recently, preventative strategies for chikungunya were largely ineffective, relying on vector control and individual avoidance of mosquito bites.

Methods: This review outlines the preclinical and clinical efficacy and safety data that led to the approval of VLA1553 (IXCHIQ®), a live-attenuated vaccine against chikungunya disease.

Safety and immunogenicity of a live-attenuated chikungunya virus vaccine in endemic areas of Brazil: interim results of a double-blind, randomised, placebo-controlled phase 3 trial in adolescents.

Background: Chikungunya outbreaks have been reported in Brazil since 2014. Adolescents are a sensitive population who would benefit from a prophylactic vaccine. This study assessed the immunogenicity and safety of the vaccine VLA1553 in adolescents in Brazil.

Antibody persistence and safety of a live-attenuated chikungunya virus vaccine up to 2 years after single-dose administration in adults in the USA: a single-arm, multicentre, phase 3b study.

Background: Chikungunya virus infection can lead to long-term debilitating symptoms. A precursor phase 3 clinical study showed high seroprotection (defined as a 50% plaque reduction of chikungunya virus-specific neutralising antibodies on a micro plaque reduction neutralisation test [μPRNT] titre of ≥150 in baseline seronegative participants) up to 6 months after a single vaccination of the chikungunya virus vaccine VLA1553 (Valneva Austria, Vienna, Austria) and a good safety profile. Here we report antibody persistence and safety up to 2 years.

Combined immunogenicity evaluation for a new single-dose live-attenuated chikungunya vaccine.

Background: Chikungunya is a serious and debilitating viral infection with a significant disease burden. VLA1553 (IXCHIQ®) is a live-attenuated vaccine licensed for active immunization for prevention of disease caused by chikungunya virus (CHIKV).

Methods: Immunogenicity following a single dose of VLA1553 was evaluated in healthy adults aged ≥18 years in two Phase 3 trials [N = 656 participants (per protocol analysis set)].

A randomized, double-blinded Phase 3 study to demonstrate lot-to-lot consistency and to confirm immunogenicity and safety of the live-attenuated chikungunya virus vaccine candidate VLA1553 in healthy adults†.

Background: The global spread of the chikungunya virus (CHIKV) increases the exposure risk for individuals travelling to or living in endemic areas. This Phase 3 study was designed to demonstrate manufacturing consistency between three lots of the single shot live-attenuated CHIKV vaccine VLA1553, and to confirm the promising immunogenicity and safety data obtained in previous trials.

Methods: This randomized, double-blinded, lot-to-lot consistency, Phase 3 study, assessed immunogenicity and safety of VLA1553 in 408 healthy adults (18-45 years) in 12 sites across the USA.

Safety and immunogenicity of a novel multivalent OspA-based vaccine candidate against Lyme borreliosis: a randomised, phase 1 study in healthy adults.

Background: Lyme borreliosis, potentially associated with serious long-term complications, is caused by the species complex Borrelia burgdorferi sensu lato. We investigated a novel Lyme borreliosis vaccine candidate (VLA15) targeting the six most common outer surface protein A (OspA) serotypes 1-6 to prevent infection with pathogenic Borrelia spp prevalent in Europe and North America.

Methods: This was a partially randomised, observer-masked, phase 1 study in healthy adults older than 18 years to younger than 40 years (n=179) done in trial sites in Belgium and the USA.

Safety and immunogenicity against ancestral, Delta and Omicron virus variants following a booster dose of an inactivated whole-virus COVID-19 vaccine (VLA2001): Interim analysis of an open-label extension of the randomized, controlled, phase 3 COV-COMPARE trial.

Objectives: Booster doses for COVID-19 vaccinations have been shown to amplify the waning immune response after primary vaccination and to enhance protection against emerging variants of concern (VoCs). Here, we aimed to assess the immunogenicity and safety of a booster dose of an inactivated whole-virus COVID-19 vaccine (VLA2001) after primary vaccination with 2 doses of either VLA2001 or ChAdOx1-S (Oxford-Astra Zeneca), including the cross-neutralization capacity against the Delta and Omicron VoCs.

Methods: This interim analysis of an open-label extension of a randomized, controlled phase 3 trial assessed a single booster dose of an inactivated whole-virus COVID-19 vaccine (VLA2001) in healthy or medically stable adults aged 18 years and above, recruited in 21 clinical sites in the UK, who had previously received two doses of either VLA2001 or ChAdOx1-S.

Safety and immunogenicity of a single-shot live-attenuated chikungunya vaccine: a double-blind, multicentre, randomised, placebo-controlled, phase 3 trial.

Background: VLA1553 is a live-attenuated vaccine candidate for active immunisation and prevention of disease caused by chikungunya virus. We report safety and immunogenicity data up to day 180 after vaccination with VLA1553.

Methods: This double-blind, multicentre, randomised, phase 3 trial was done in 43 professional vaccine trial sites in the USA.

A randomized, placebo-controlled, blinded phase 1 study investigating a novel inactivated, Vero cell-culture derived Zika virus vaccine.

Background: Zika virus (ZIKV) is an emerging public health threat, rendering development of a safe and effective vaccine against the virus a high priority to face this unmet medical need. Our vaccine candidate has been developed on the same platform used for the licensed vaccine IXIARO®, a vaccine against Japanese Encephalitis virus, another closely related member of the Flaviviridae family.

Methods: Between 24 February 2018 and 16 November 2018, we conducted a randomized, observer-blinded, placebo controlled, single center phase 1 study to assess the safety and immunogenicity of an adjuvanted, inactivated, purified whole-virus Zika vaccine candidate in the USA.

Immunogenicity and safety of an inactivated whole-virus COVID-19 vaccine (VLA2001) compared with the adenoviral vector vaccine ChAdOx1-S in adults in the UK (COV-COMPARE): interim analysis of a randomised, controlled, phase 3, immunobridging trial.

Background: The Valneva COVID-19 vaccine (VLA2001; Valneva Austria, Vienna, Austria) is an inactivated whole-virus, adjuvanted SARS-CoV-2 vaccine. We aimed to assess the safety and immunogenicity of primary vaccination with VLA2001 versus the ChAdOx1-S (Oxford-AstraZeneca) adenoviral-vectored vaccine.

Methods: In this immunobridging phase 3 trial (COV-COMPARE), participants aged 18 years and older who were medically stable (as determined by an investigator) were enrolled at 26 sites in the UK.

Safety and immunogenicity of the inactivated whole-virus adjuvanted COVID-19 vaccine VLA2001: A randomized, dose escalation, double-blind phase 1/2 clinical trial in healthy adults.

Objectives: We aimed to evaluate the safety and optimal dose of a novel inactivated whole-virus adjuvanted vaccine against SARS-CoV-2: VLA2001.

Methods: We conducted an open-label, dose-escalation study followed by a double-blind randomized trial using low, medium and high doses of VLA2001 (1:1:1). The primary safety outcome was the frequency and severity of solicited local and systemic reactions within 7 days after vaccination.

Single-shot live-attenuated chikungunya vaccine in healthy adults: a phase 1, randomised controlled trial.

Background: Chikungunya disease, which results in incapacitating arthralgia, has been reported worldwide. We developed a live-attenuated chikungunya virus (CHIKV) vaccine candidate designed for active immunisation of the general population living in endemic regions, as well as serving as a prophylactic measure for travellers to endemic areas.

Methods: This single-blind, randomised, dose-escalation, phase 1 study investigated as primary outcome safety of a live-attenuated CHIKV vaccine candidate.

Neutralizing antibody persistence in pediatric travelers from non-JE-endemic countries following vaccination with IXIARO® Japanese encephalitis vaccine: An uncontrolled, open-label phase 3 follow-up study.

Background: In an initial study among children from non-Japanese encephalitis (JE)-endemic countries, seroprotection rates remained high 6 months after completion of the primary series with IXIARO®.

Methods: In this open-label follow-up study, a subset of 23 children who received a 2-dose primary series of IXIARO® in the parent study, were evaluated for safety and neutralizing antibody persistence for 36 months.

Results: Seroprotection rates (SPRs) remained high but declined from 100% one month after primary immunization to 91.

Efficacy, immunogenicity, and safety of IC43 recombinant Pseudomonas aeruginosa vaccine in mechanically ventilated intensive care patients-a randomized clinical trial.

Background: Pseudomonas aeruginosa infections are a serious threat in intensive care units (ICUs). The aim of this confirmatory, randomized, multicenter, placebo-controlled, double-blind, phase 2/3 study was to assess the efficacy, immunogenicity, and safety of IC43 recombinant Pseudomonas aeruginosa vaccine in non-surgical ICU patients.

Methods: Eight hundred patients aged 18 to 80 years admitted to the ICU with expected need for mechanical ventilation for ≥ 48 h were randomized 1:1 to either IC43 100 μg or saline placebo, given in two vaccinations 7 days apart.

Persistence of the immune response after vaccination with the Japanese encephalitis vaccine, IXIARO® in healthy adults: A five year follow-up study.

Immunization with the Japanese encephalitis (JE) vaccine IXIARO® results in protective neutralizing antibody levels for one year. Since persistence of protective titer levels beyond one year was unknown, a 5 years follow-up study was conducted. Additionally, data were stratified to compare the persistence of protective neutralizing antibodies against JE in people with or without tick-borne encephalitis (TBE) vaccination.

Antibody Persistence up to 3 Years After Primary Immunization With Inactivated Japanese Encephalitis Vaccine IXIARO in Philippine Children and Effect of a Booster Dose.

Background: An inactivated Vero cell culture derived Japanese encephalitis virus vaccine (IXIARO) requires a booster dose 1 year after primary schedule for long-term antibody persistence in adults. The aim of this study is to evaluate immunogenicity and safety of a booster dose in children 2 months to <18 years of age.

Methods: This is a randomized, controlled open-label study in the Philippines.

Safety and immunogenicity of an inactivated Vero cell_derived Japanese encephalitis vaccine (IXIARO, JESPECT) in a pediatric population in JE non-endemic countries: An uncontrolled, open-label phase 3 study.

Background: Young travelers to South-East Asia may be at risk for Japanese encephalitis (JE).

Methods: IXIARO (0.25 ml or 0.

Immunogenicity and safety of the inactivated Japanese encephalitis vaccine IXIARO® in elderly subjects: Open-label, uncontrolled, multi-center, phase 4 study.

Background: IXIARO® is a Vero cell-derived, inactivated Japanese encephalitis (JE) vaccine licensed mainly in western countries for children and adults traveling to JE endemic areas. Limited immunogenicity and safety data in elderly travelers have been available.

Objectives: To evaluate safety and immunogenicity of IXIARO in elderly subjects.

Safety, immunogenicity and dose response of VLA84, a new vaccine candidate against Clostridium difficile, in healthy volunteers.

Background: Clostridium difficile infection (CDI) is the leading cause of antibiotic-associated diarrhoea and colitis and the most common pathogen of health care-associated infections. In the US, CDI causes approximately half a million infections and close to 30,000 deaths. Despite antibiotic treatment of C.