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Iohann Boulay

Bio: Iohann Boulay is an academic researcher. The author has contributed to research in topics: Immunogenicity & Medicine. The author has an hindex of 3, co-authored 4 publications receiving 71 citations.

Papers
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Journal ArticleDOI
TL;DR: In this paper, the authors report Day 42 interim safety and immunogenicity data from an observer-blinded, dose escalation, randomized controlled study of a virus-like particle vaccine candidate produced in plants that displays the SARS-CoV-2 spike glycoprotein (CoVLP: NCT04450004 ).
Abstract: Several severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are being deployed, but the global need greatly exceeds the supply, and different formulations might be required for specific populations. Here we report Day 42 interim safety and immunogenicity data from an observer-blinded, dose escalation, randomized controlled study of a virus-like particle vaccine candidate produced in plants that displays the SARS-CoV-2 spike glycoprotein (CoVLP: NCT04450004 ). The co-primary outcomes were the short-term tolerability/safety and immunogenicity of CoVLP formulations assessed by neutralizing antibody (NAb) and cellular responses. Secondary outcomes in this ongoing study include safety and immunogenicity assessments up to 12 months after vaccination. Adults (18–55 years, n = 180) were randomized at two sites in Quebec, Canada, to receive two intramuscular doses of CoVLP (3.75 μg, 7.5 μg, and 15 μg) 21 d apart, alone or adjuvanted with AS03 or CpG1018. All formulations were well tolerated, and adverse events after vaccination were generally mild to moderate, transient and highest in the adjuvanted groups. There was no CoVLP dose effect on serum NAbs, but titers increased significantly with both adjuvants. After the second dose, NAbs in the CoVLP + AS03 groups were more than tenfold higher than titers in Coronavirus 2019 convalescent sera. Both spike protein-specific interferon-γ and interleukin-4 cellular responses were also induced. This pre-specified interim analysis supports further evaluation of the CoVLP vaccine candidate. Safety and immunogenicity results in humans of a two-dose SARS-CoV-2 vaccine made from plants support further assessment of potential efficacy.

156 citations

Journal ArticleDOI
TL;DR: The CoVLP+AS03 vaccine was effective in preventing Covid-19 caused by a spectrum of variants, with efficacy ranging from 69.5% against symptomatic infection to 78.8% against moderate-to-severe disease.
Abstract: Abstract Background Coronavirus-like particles (CoVLP) that are produced in plants and display the prefusion spike glycoprotein of the original strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are combined with an adjuvant (Adjuvant System 03 [AS03]) to form the candidate vaccine. Methods In this phase 3, multinational, randomized, placebo-controlled trial conducted at 85 centers, we assigned adults (≥18 years of age) in a 1:1 ratio to receive two intramuscular injections of the CoVLP+AS03 vaccine or placebo 21 days apart. The primary objective of the trial was to determine the efficacy of the CoVLP+AS03 vaccine in preventing symptomatic coronavirus disease 2019 (Covid-19) beginning at least 7 days after the second injection, with the analysis performed after the detection of at least 160 cases. Results A total of 24,141 volunteers participated in the trial; the median age of the participants was 29 years. Covid-19 was confirmed by polymerase-chain-reaction assay in 165 participants in the intention-to-treat population; all viral samples that could be sequenced contained variants of the original strain. Vaccine efficacy was 69.5% (95% confidence interval [CI], 56.7 to 78.8) against any symptomatic Covid-19 caused by five variants that were identified by sequencing. In a post hoc analysis, vaccine efficacy was 78.8% (95% CI, 55.8 to 90.8) against moderate-to-severe disease and 74.0% (95% CI, 62.1 to 82.5) among the participants who were seronegative at baseline. No severe cases of Covid-19 occurred in the vaccine group, in which the median viral load for breakthrough cases was lower than that in the placebo group by a factor of more than 100. Solicited adverse events were mostly mild or moderate and transient and were more frequent in the vaccine group than in the placebo group; local adverse events occurred in 92.3% and 45.5% of participants, respectively, and systemic adverse events in 87.3% and 65.0%. The incidence of unsolicited adverse events was similar in the two groups up to 21 days after each dose (22.7% and 20.4%) and from day 43 through day 201 (4.2% and 4.0%). Conclusions The CoVLP+AS03 vaccine was effective in preventing Covid-19 caused by a spectrum of variants, with efficacy ranging from 69.5% against symptomatic infection to 78.8% against moderate-to-severe disease. (Funded by Medicago; ClinicalTrials.gov number, NCT04636697.)

62 citations

Posted ContentDOI
06 Nov 2020-medRxiv
TL;DR: In this article, the authors evaluated the safety, tolerability, and immunogenicity of CoVLP at three dose levels (3.75 microgram, 7.5 microgram and 15 microgram) unadjuvanted or adjuvanted with either CpG 1018 or AS03.
Abstract: Background: The stabilized prefusion form of the SARS-CoV-2 spike protein is produced by transient expression in Nicotiana benthamiana. The trimeric spike glycoproteins are displayed at the surface of self-assembling Virus-Like-Particles that mimic the shape and the size of the virus. The candidate vaccine (CoVLP) administered alone or with AS03 or CpG1018 adjuvants was evaluated in a Phase 1 trial in healthy adults. (ClinicalTrials.gov number NCT04450004) Methods: The study was a randomized, partially-blinded, prime-boost 21 days apart, dose-escalation Phase 1 study intended to assess the safety, tolerability, and immunogenicity of CoVLP at three dose levels (3.75 microgram, 7.5 microgram, and 15 microgram) unadjuvanted or adjuvanted with either CpG 1018 or AS03 in 180 SARS-CoV-2 seronegative healthy adults 18 to 55 years of age. Enrollment was staggered for dose-escalation. At each dose level, the vaccine was initially administered to a small number of subjects. Vaccination of the remaining subjects at the same dose level and the next higher vaccine dose level was administered with approval of an Independent Data Monitoring Committee (IDMC). The same procedure was followed for the second vaccine administration. Monitoring of safety signals was performed throughout the study with pre-determined pausing/stopping rules if there was clear evidence of harmful effects such as severe adverse events (AEs) related to the treatment. The primary endpoints were the safety and tolerability of the vaccine after each dose and the immunogenicity as assessed by neutralizing antibody responses assessed using a vesicular stomatitis virus (VSV) pseudovirion assay and interferon-gamma and interleukin-4 (IL-4) ELISpot assays at Days 0, 21 and 42. Secondary endpoints were anti-spike antibody responses by ELISA and neutralizing antibodies measured by live virus plaque reduction neutralization test (PRNT) assay at Days 0, 21 and 42 and immunogenicity with additional safety and immunogenicity endpoints planned for 6-months following the last vaccination. The anti-spike and neutralizing antibody responses were compared with 23 convalescent serum samples from symptomatic Covid-19 patients. We performed a primary analysis at day 42. Results: A total of 180 subjects (102 females: 78 males: average 34.3 years) were recruited to the study and interim safety and immunogenicity data up to day 42 after the first dose are reported here. There was no obvious CoVLP dose effect in safety outcomes for any of the formulations tested and all formulations were generally well-tolerated. Most solicited local and systemic AEs were mild-moderate and transient. Reactogenicity was increased in all adjuvanted formulations and was generally highest in the CoVLP+AS03 groups. Local and systemic adverse events were reported with similar frequency after the first and second doses in subjects who received either CoVLP alone or CoVLP+CpG1018 but increased in both frequency and severity after the second dose in the CoVLP+AS03 groups. CoVLP alone only elicited a weak total anti-spike IgG response at the highest dose level and little-to-no neutralization antibody response, even after the second dose. Cellular responses in the CoVLP alone groups (IFN-gamma and IL-4) were detectable after the second dose but were still only marginally above background levels. The addition of either adjuvant substantially increased both antibody and cellular responses at most CoVLP dose levels and changes were most pronounced after the second dose. However, a substantial neutralizing antibody response after the first dose was only seen in all CoVLP+AS03 groups. After the second dose, both total anti-spike IgG and neutralizing antibody titers in the CoVLP+AS03 groups were higher than those in the CoVLP+CpG1018 groups. The antibody titers achieved were either similar to (CoVLP+CpG1018) or at least 10-times higher (CoVLP+AS03) than those seen in convalescent plasma. Administration of CoVLP with either adjuvant also significantly increased the cellular responses. After 2 doses, both IFN-gamma and IL-4 responses were significantly increased in the CoVLP+CpG1018 groups. In the CoVLP+AS03 groups, significant increases in the cellular responses were observed after the first dose while IFN-gamma and IL-4 increased further in both magnitude and number of subjects responding after the second dose. Again, the cellular responses in the CoVLP+AS03 groups were higher than those seen in the CoVLP+CpG1018 groups. Conclusion: These data demonstrate that CoVLP administered with either CpG1018 or AS03 has a safety profile similar to other candidate vaccines for SARS-CoV-2. When administered with either AS03 or CpG1018, several of the CoVLP dose levels elicited strong humoral and T cell responses after the second dose. When administered with AS03, even the 3.75 microgram CoVLP dose elicited neutralizing antibody titers that were ~10-times higher than those observed in individuals recovering from Covid-19 as well as consistent and balanced IFN-gamma and IL-4 responses. Although many CoVLP formulations were immunogenic, in the absence of established correlates of protection and given the advantages of dose-sparing in the context of the on-going pandemic, these findings suggest that CoVLP (3.75 microgram)+AS03 has a good benefit/risk ratio and support the transition of this formulation to studies in expanded populations and to efficacy evaluations

54 citations

Posted ContentDOI
17 May 2021-medRxiv
TL;DR: In this article, the authors present interim safety and immunogenicity data from a Phase 2, randomized, placebo-controlled trial in Adults aged 18+ immunized with a virus-like particle vaccine candidate produced in plants displaying SARS-CoV-2 spike glycoprotein (CoVLP) adjuvanted with AS03.
Abstract: The rapid spread of SARS-CoV-2 globally continues to impact humanity on a global scale with rising morbidity and mortality. Despite the development of multiple effective vaccines, new vaccines continue to be required to supply ongoing demand. We report Day 42 interim safety and immunogenicity data from a Phase 2, randomized, placebo-controlled trial in Adults aged 18+ immunized with a virus-like particle vaccine candidate produced in plants displaying SARS-CoV-2 spike glycoprotein (CoVLP) adjuvanted with AS03 (NCT04636697). This report focuses on presenting safety, tolerability and immunogenicity, as measured by neutralizing antibody (NAb) and cell mediated immunity (IFN-{gamma} and IL-4 ELISpot) responses, in Adults aged 18-64 (Adults) and Older Adults aged 65+ (Older Adults). CoVLP adjuvanted with AS03 was well-tolerated and adverse events (AE) were primarily mild or moderate and of transient duration. AEs in Older Adults were more limited than those observed in the Adult population. CoVLP with AS03 induced a significant humoral immune response in both age cohorts. CoVLP with AS03 induced a greater humoral response in Adults than Older Adults after a single dose but this effect was overcome with a second dose when both age cohorts responded with NAb titers that were [~]10-fold higher than those in a panel of sera from patients recovering from COVID-19. A single dose of CoVLP with AS03 induced a significant IFN-{gamma} response in both age cohorts; a second dose significantly boosted IFN-{gamma} and IL-4 responses in both age cohorts. Adults generated a stronger IFN-{gamma} and IL-4 cellular response than did Older Adults after one or two doses of AS03-adjuvanted CoVLP. Safety and immunogenicity from Adults with comorbidities as well as final safety and immunogenicity responses after 12 months will be reported upon availability.

25 citations

Posted ContentDOI
26 Jan 2022-medRxiv
TL;DR: The primary efficacy endpoint was prevention of symptomatic SARS-CoV-2 infection with onset at least 7 days after the second injection and was triggered by the identification of [≥]160 virologically-confirmed cases, and tolerability and safety of CoVLP+AS03 were also determined.
Abstract: Background: Several COVID-19 vaccines are currently being deployed but supply constraints, concerns over durability of immune responses, solidifying vaccine hesitancy/resistance and vaccine efficacy in the face of emerging variants mean that new vaccines continue to be needed to fight the ongoing pandemic. The vaccine described here is an enveloped, coronavirus-like particle produced in plants (CoVLP) that displays the prefusion-stabilized spike (S) glycoprotein of SARS-CoV-2 (ancestral Wuhan strain) and is adjuvanted with AS03 (CoVLP+AS03). Methods: This Phase 3 randomized, observer-blind, placebo-controlled trial was conducted at 85 centers in Argentina, Brazil, Canada, Mexico, the UK, and the USA. Adults [≥]18 years of age including those at high risk for COVID-19 complications were randomly assigned 1:1 to receive two intramuscular injections of CoVLP (3.75 g) adjuvanted with AS03 or placebo, 21 days apart. The primary efficacy endpoint was prevention of symptomatic ([≥] 1 symptom), PCR-confirmed SARS-CoV-2 infection with onset at least 7 days after the second injection and was triggered by the identification of [≥]160 virologically-confirmed cases. Tolerability and safety of CoVLP+AS03 were also determined. Results: A total of 24,141 volunteers were randomly assigned 1:1 to receive vaccine or placebo (N= 12,074 and 12,067, respectively: median age 29, range 18 to 86 years). Overall, 83% received both doses. 14.8% were SARS-CoV-2 seropositive at baseline. Symptomatic SARS-CoV-2 infection was confirmed in 165 study participants in the intention to treat (ITT) set and 157 in the per-protocol population (PP) set. Of the 157 in the PP set, 118 COVID-19 cases were in the placebo group and 39 COVID-19 cases were in the CoVLP+AS03 group for an overall vaccine efficacy (VE) of 71.0% (95% confidence interval (CI) 58.6, 80.0). Moderate-to-severe COVID-19 occurred in 8 and 32 participants in the CoVLP+AS03 and placebo groups, respectively: VE 78.1% (95% CI: 53.9, 90.5) in the PP set overall and 84.5% (95% CI: 62.0, 94.7) in those seronegative at recruitment. To date, 100% of the sequenced strains (122/165 cases: 73.39%) were variants, dominated by Delta (45.9%) and Gamma (43.4%) strains. Vaccine efficacy by variant was 75.3% (95% CI 52.8, 87.9) against Delta and 88.6% (95% CI 74.6, 95.6) against Gamma. Cross-protection was also observed against Alpha, Lambda and Mu variants; although fewer cases were identified, all were in the placebo group. At diagnosis, viral loads in the CoVLP+AS03 breakthrough cases were >100-fold lower than in the placebo cases. Reactogenicity data for solicited adverse events (AEs) was analysed for a subset (N=4,136 in vaccine arm and N=3,683 for placebo) of participants. Reactogenicity was mostly mild to moderate, and transient, and occurred more frequently in the CoVLP+AS03 group. The safety analysis set used for unsolicited AE assessment comprised 24,076 participants who received at least one study injection: 12,036 received CoVLP+AS03 and 12,040 received placebo. All serious adverse events were assessed as unrelated, except two events reported in the same subject in the placebo group. No significant imbalance or safety concern was noted in medically attended AEs (MAAEs), adverse event of special interest (AESIs), AEs leading to withdrawal, deaths, or adverse events potentially associated with currently authorized vaccines. Conclusions: The CoVLP+AS03 vaccine candidate conferred an efficacy of 71.0% in preventing symptomatic SARS-CoV-2 infection caused by a spectrum of variants. Vaccine efficacy of 78.1% was observed against moderate and severe disease, while variant-specific efficacy ranged from 75.3% to 100%. Markedly lower viral loads in the CoVLP+AS03 group at the time of diagnosis suggests a significant virologic impact of vaccination even in the breakthrough cases. CoVLP+AS03 vaccine candidate was well tolerated, and no safety concerns were identified during the study. If approved by regulators, this more traditional protein+adjuvant vaccine produced using the novel plant-based platform may be able to make an important contribution to the global struggle against the increasingly complex family of SARS-CoV-2 viruses (Funded by Medicago with grants from the governments of Quebec and Canada; NCT04636697).

6 citations


Cited by
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Journal ArticleDOI
22 Feb 2021
TL;DR: The SARS-CoV-2 virus is an RNA virus that belongs to the Coronaviridae family and causes COVID-19 disease, which caused more than 1,866,000 deaths as discussed by the authors.
Abstract: The new SARS-CoV-2 virus is an RNA virus that belongs to the Coronaviridae family and causes COVID-19 disease. The newly sequenced virus appears to originate in China and rapidly spread throughout the world, becoming a pandemic that, until January 5th, 2021, has caused more than 1,866,000 deaths. Hence, laboratories worldwide are developing an effective vaccine against this disease, which will be essential to reduce morbidity and mortality. Currently, there more than 64 vaccine candidates, most of them aiming to induce neutralizing antibodies against the spike protein (S). These antibodies will prevent uptake through the human ACE-2 receptor, thereby limiting viral entrance. Different vaccine platforms are being used for vaccine development, each one presenting several advantages and disadvantages. Thus far, thirteen vaccine candidates are being tested in Phase 3 clinical trials; therefore, it is closer to receiving approval or authorization for large-scale immunizations.

421 citations

Journal ArticleDOI
TL;DR: A review of the known knowns and known unknowns of adjuvants can be found in this article, where the authors discuss emerging concepts and highlight how our expanding knowledge about innate immunity and systems vaccinology are revitalizing the science and development of novel adjuants for use in vaccines against COVID-19 and future pandemics.
Abstract: Adjuvants are vaccine components that enhance the magnitude, breadth and durability of the immune response. Following its introduction in the 1920s, alum remained the only adjuvant licensed for human use for the next 70 years. Since the 1990s, a further five adjuvants have been included in licensed vaccines, but the molecular mechanisms by which these adjuvants work remain only partially understood. However, a revolution in our understanding of the activation of the innate immune system through pattern recognition receptors (PRRs) is improving the mechanistic understanding of adjuvants, and recent conceptual advances highlight the notion that tissue damage, different forms of cell death, and metabolic and nutrient sensors can all modulate the innate immune system to activate adaptive immunity. Furthermore, recent advances in the use of systems biology to probe the molecular networks driving immune response to vaccines ('systems vaccinology') are revealing mechanistic insights and providing a new paradigm for the vaccine discovery and development process. Here, we review the 'known knowns' and 'known unknowns' of adjuvants, discuss these emerging concepts and highlight how our expanding knowledge about innate immunity and systems vaccinology are revitalizing the science and development of novel adjuvants for use in vaccines against COVID-19 and future pandemics.

390 citations

Journal ArticleDOI
06 May 2021-Vaccine
TL;DR: The current study systematically reviewed, summarized and meta-analyzed the clinical features of the vaccines in clinical trials to provide a better estimate of their efficacy, side effects and immunogenicity and found the adenovirus-vectored and mRNA-based vaccines showed the highest efficacy after first and second doses, respectively.

203 citations

Journal ArticleDOI
TL;DR: In this article, a multidisciplinary group of international experts in anaphylaxis composed of allergy, infectious disease, emergency medicine, and front-line clinicians to systematically develop recommendations regarding SARS-CoV-2 vaccine immediate allergic reactions.

131 citations

Journal ArticleDOI
TL;DR: In this article, a comprehensive overview of the safety profile of COVID-19 vaccines by using meta-analysis technique was provided by using PubMed, Embase, Web of Science, PMC, official regulatory websites, and post-authorization safety surveillance data.
Abstract: BACKGROUND: The rapid process of research and development and lack of follow-up time post-vaccination aroused great public concern about the safety profile of COVID-19 vaccine candidates. To provide comprehensive overview of the safety profile of COVID-19 vaccines by using meta-analysis technique. METHODS: English-language articles and results posted on PubMed, Embase, Web of Science, PMC, official regulatory websites, and post-authorization safety surveillance data were searched through June 12, 2021. Publications disclosing safety data of COVID-19 candidate vaccines in humans were included. A meta-analysis of proportions was performed to estimate the pooled incidence and the pooled rate ratio (RR) of safety outcomes of COVID-19 vaccines using different platforms. RESULTS: A total of 87 publications with safety data from clinical trials and post-authorization studies of 19 COVID-19 vaccines on 6 different platforms were included. The pooled rates of local and systemic reactions were significantly lower among inactivated vaccines (23.7%, 21.0%), protein subunit vaccines (33.0%, 22.3%), and DNA vaccines (39.5%, 29.3%), compared to RNA vaccines (89.4%, 83.3%), non-replicating vector vaccines (55.9%, 66.3%), and virus-like particle vaccines (100.0%, 78.9%). Solicited injection-site pain was the most common local reactions, and fatigue and headache were the most common systemic reactions. The frequency of vaccine-related serious adverse events was low (< 0.1%) and balanced between treatment groups. Vaccine platforms and age groups of vaccine recipients accounted for much of the heterogeneity in safety profiles between COVID-19 vaccines. Reporting rates of adverse events from post-authorization observational studies were similar to results from clinical trials. Crude reporting rates of adverse events from post-authorization safety monitoring (passive surveillance) were lower than in clinical trials and varied between countries. CONCLUSIONS: Available evidence indicates that eligible COVID-19 vaccines have an acceptable short-term safety profile. Additional studies and long-term population-level surveillance are strongly encouraged to further define the safety profile of COVID-19 vaccines.

117 citations