The investigational
vaccine (1790GAHB) based on GMMA (generalized modules for membrane antigens) is immunogenic, with an acceptable safety profile in adults. However, pre-vaccination anti-
...lipopolysaccharide (LPS) antibody levels seemed to impact vaccine-related immune responses. This phase 1, open-label, non-randomized extension study (ClinicalTrials.gov: NCT03089879) evaluated immunogenicity of a 1790GAHB booster dose in seven adults with undetectable antibodies prior to priming with three 1790GAHB vaccinations 2-3 years earlier (boosted group), compared to one dose in 28 vaccine-naïve individuals (vaccine-naïve group). Anti-
LPS serum IgG geometric mean concentrations and seroresponse (increase of ≥25 EU or ≥50% from baseline antibody ≤ 50 EU and ≥50 EU, respectively) rates were calculated at vaccination (day D1), D8, D15, D29, D85. Safety was assessed. Geometric mean concentrations at D8 were 168 EU (boosted group) and 32 EU (vaccine-naïve group). Response peaked at D15 (883 EU) and D29 (100 EU) for the boosted and vaccine-naïve groups. Seroresponse rates at D8 were 86% (boosted group) and 24% (vaccine-naïve group) and increased at subsequent time points. Across both groups, pain (local) and fatigue (systemic) were the most frequent solicited adverse events (AEs). Unsolicited AEs were reported by 57% of boosted and 25% of vaccine-naïve participants. No deaths, serious AEs, or AEs of special interest (except one mild neutropenia case, possibly vaccination-related) were reported. One 1790GAHB dose induced a significant booster response in previously-primed adults, regardless of priming dose, and strong immune response in vaccine-naïve individuals. Vaccination was well tolerated.
This study aimed to compare the humoral responses to mRNA COVID-19 vaccination in people living with HIV (PWH) and HIV-negative individuals.
We included PWH with an undetectable viral load under ART ...and HIV-negative participants from the French nationwide ANRS COV-POPART cohort who had received two doses of vaccine as a primary vaccination. We compared humoral response between controls and PWH, stratified by CD4 cell count (<200/mm3 and ≥200/mm3 CD4 cell counts) at 1, 6, and 12 months after primary vaccination.
A total of 1776 participants were included in this analysis, 684 PWH (99% were on ART, median CD4 counts 673 cells/mm3) and 1092 controls. At 1 month, after adjustment on age, sex, and BMI, PWH had lower seroneutralization titers than controls, and PWH with <200 CD4 cell/mm3 had lower anti-Spike SARS-CoV-2 IgG antibodies. Same results were found at 6 months. However, in participants who received a booster dose between 6 and 12 months postprimary vaccination, we did not observe differences between PWH and controls at 12 months.
PWH had high responses to primary mRNA COVID-19 vaccination. In those who received a booster dose after 6 months, the humoral response at 12 months increased to similar levels to controls, even in those with low CD4 counts at baseline.
Approximately 164,000 deaths yearly are due to shigellosis, primarily in developing countries. Thus, a safe and affordable Shigella vaccine is an important public health priority. The GSK Vaccines ...Institute for Global Health (GVGH) developed a candidate Shigella sonnei vaccine (1790GAHB) using the Generalized Modules for Membrane Antigens (GMMA) technology. The paper reports results of 1790GAHB Phase 1 studies in healthy European adults.
To evaluate the safety and immunogenicity profiles of 1790GAHB, we performed two parallel, phase 1, observer-blind, randomized, placebo-controlled, dose escalation studies in France (“study 1”) and the United Kingdom (“study 2”) between February 2014 and April 2015 (ClinicalTrials.gov, number NCT02017899 and NCT02034500, respectively) in 18–45years old subjects (50 in study 1, 52 in study 2). Increasing doses of Alhydrogel adsorbed 1790, expressed by both O Antigen (OAg) and protein quantity, or placebo were given either by intramuscular route (0.059/1, 0.29/5, 1.5/25, 2.9/50, 5.9/100μg of OAg/μg of protein; study 1) or by intradermal (ID), intranasal (IN) or intramuscular (IM) route of immunization (0.0059/0.1, 0.059/1, 0.59/10μg ID, 0.29/5, 1.2/20, 4.8/80μg IN and 0.29/5μg IM, respectively; study 2). In absence of serologic correlates of protection for Shigella sonnei, vaccine induced immunogenicity was compared to anti-LPS antibody in a population naturally exposed to S. sonnei.
Vaccines were well tolerated in both studies and no death or vaccine related serious adverse events were reported. In study 1, doses ≥1.5/25μg elicited serum IgG median antibody greater than median level in convalescent subjects after the first dose. No vaccine group in study 2 achieved median antibody greater than the median convalescent antibody.
Intramuscularly administered Shigella sonnei GMMA vaccine is well tolerated, up to and including 5.9/100μg and induces antibody to the OAg of at least the same magnitude of those observed following natural exposure to the pathogen. Vaccine administered by ID or IN, although well tolerated, is poorly immunogenic at the doses delivered. The data support the use of the GMMA technology for the development of intramuscular multivalent Shigella vaccines.
•GVGH GMMA vaccine against S. sonnei was well tolerated by IM, IN and ID routes of immunization in young European adults.•Doses ≥1.5/25μg elicited serum IgG median antibody greater than median level in convalescent subjects after the first dose.•Clinical data support the use of the GMMA technology for the development of intramuscular Shigella multivalent vaccines.
Shigellosis is an important cause of diarrhoea especially in children of developing countries. No vaccine is available. Based on the 2015 Global Burden of Disease, Shigella caused approximately 164,000 deaths due to diarrhoea in 2015, supporting the public health relevance of the disease and the need for a vaccine. The GMMA (Generalized Modules for Membrane Antigens) technology was used for the development of a vaccine against Shigella sonnei which, tested in these trials for the first time, was shown to be well tolerated in young adults and induced specific antibody titres at least as high as after natural infection.
In May 2021, while the immunization campaign was in progress, the emergence of new SARS-CoV-2 variants led us to assess attitudes toward participation in a COVID-19 vaccine clinical trial (VCT) in ...France. Between the 10th and the 23rd of May 2021, we conducted a cross-sectional online survey among a representative sample of the French population aged 18 and over and a specific sample of the French population over 65. Among the 3,056 respondents, 28.0% (856) would consider participation in a COVID-19 VCT. Factors independently negatively associated with willingness to participate in a COVID-19 VCT were female gender with an adjusted odd ratio (aOR) 0.42 and 95% confidence interval (95% CI) 0.35-0.51, and mistrust in health actors (in their own physician and pharmacists, health ministry, government, scientists in medias, medias and pharmaceutical companies) with aOR 0.86 (95% CI 0.84-0.88) by one-point increase in mistrust in health actors score. Factors positively associated with willingness to participate in a COVID-19 VCT were COVID-19 vaccination or intention to get vaccinated with aOR 4.89 (95% CI 3.15-7.61), being a healthcare worker with aOR 2.051 (95% CI 1.51-2.80), being at risk for severe COVID-19 with aOR 1.39 (95% CI 1.14-1.69) and altruism as the main reason for getting vaccination with aOR 1.56 (95% CI 1.29-1.88). In May 2021, despite COVID 19 vaccine availability, 28% of the French population would agree to participate in a COVID-19 VCT. Mistrust in health actors contributes to a reduction in the intention to participate. Attitudes toward COVID-19 vaccination predict attitudes toward participation in a COVID-19 VCT.
Real-world studies have shown waning vaccine effectiveness against both SARS-CoV-2 infection and COVID-19-related hospitalisation within 2·5 months after a first booster dose of COVID-19 mRNA ...vaccine, especially for the SARS-CoV-2 omicron (B.1.1.529) variant.1 Several countries have thus recommended a second booster dose of COVID-19 mRNA vaccine (ie, a fourth vaccine dose) in older and immunocompromised individuals at higher risk for severe disease, hospitalisation, and death. ...humoral responses increased to similar levels in the older (≥70 years) versus younger (<70 years) age groups, with fold changes in anti-spike IgG titres between the first and second booster being higher in the older age group than in the younger age group. ...there seems to be a maximum anti-spike protein IgG titre and T-cell response (a possible ceiling effect).
Few studies have reported clinical COVID-19 sequelae six months (M6) after hospital discharge, but none has studied symptom severity.
Prevalence and severity of 7 symptoms were estimated until M6 ...using the self-administered influenza severity scale in COVID-19 hospitalized patients enrolled in the French COVID cohort. Factors associated with severity were assessed by logistic regression. Anxiety, depression and health-related quality of life (HRQL) were also assessed.
At M6, among the 324 patients (median age 61 years, 63% men, 19% admitted to intensive care during the acute phase), 187/324 (58%) reported at least one symptom, mostly fatigue (47%) and myalgia (23%). Symptom severity was scored, at most, mild in 125 (67%), moderate in 44 (23%) and severe in 18 (10%). Female gender was the sole factor associated with moderate/severe symptom reporting (OR = 1.98, 95%CI=1.13-3.47). Among the 225 patients with psychological assessment, 24 (11%) had anxiety, 18 (8%) depressive symptoms, and their physical HRQL was significantly poorer than the general population (p=0.0005).
Even if 58% of patients reported ≥1 symptom at M6, less than 7% rated any symptom as severe. Assessing symptoms severity could be helpful to identify patients requiring appropriate medical care. Women may require special attention.
Abstract
Background
In France, the increase in COVID-19 vaccine uptake among older adults slowed down between May and June 2021. Using the data from a national survey, we aimed to assess COVID-19 ...vaccine uptake among French residents aged 65 years and older, particularly at risk of severe form of the infection, and identify factors associated with non-vaccination.
Methods
A cross-sectional online survey collected the immunization status/intention to get the COVID-19 vaccine, reasons for vaccination/non-vaccination and factors potentially associated with vaccine uptake between May 10 and 23, 2021 among a large sample of French residents. Characteristics of participants were compared according to immunization status. Factors potentially associated with non-vaccination were computed into a multivariate logistic regression.
Results
Among the 1941 survey participants, 1612 (83%) reported having received at least one dose of COVID-19 vaccine. Among the 329 unvaccinated, 197 (60%) declared having the intention to get vaccinated. Younger age (adjusted odds ratio (aOR) = 1.50; 95% confidence interval (CI), 1.05–2.14), thinking previously having COVID-19 (aOR = 4.01; 95% CI, 2.17–7.40), having suffered economic impact due to the pandemic (aOR = 2.63; 95% CI, 1.71–4.04), reporting an “unsafe” opinion about COVID-19 vaccine safety (aOR = 6.79; 95% CI, 4.50–10.26), reporting an “unsupportive” opinion about vaccination in general (aOR = 4.24; 95% CI, 2.77–6.49) were independent risk factors for non-vaccination. On the other hand, trust in COVID-19 vaccine information delivered by the doctor (aOR = 0.28; 95% CI, 0.16–0.48) and trust in the government’s actions (aOR = 0.50; 95% CI, 0.34–0.74) were independent protective factors for non-vaccination. Political affiliation also remained significantly associated with vaccine uptake.
Conclusions
Despite high overall COVID-19 vaccine uptake among the study participants, differences in vaccine uptake according to the level of concerns regarding COVID-19 vaccine safety, socioeconomic profile and trust in the government were observed. Our results reinforce the importance of “reaching out” vaccination strategy that specifically targets the most vulnerable fringe of older adult population.
DNA vectors have been widely used as a priming of poxvirus vaccine in prime/boost regimens. Whether the number of DNA impacts qualitatively or quantitatively the immune response is not fully ...explored. With the aim to reinforce T-cell responses by optimizing the prime-boost regimen, the multicentric EV03/ANRS VAC20 phase I/II trial, randomized 147 HIV-negative volunteers to either 3xDNA plus 1xNYVAC (weeks 0, 4, 8 plus 24; n = 74) or to 2xDNA plus 2xNYVAC (weeks 0, 4 plus 20, 24; n = 73) groups. T-cell responses (IFN-γ ELISPOT) to at least one peptide pool were higher in the 3xDNA than the 2xDNA groups (91% and 80% of vaccinees) (P = 0.049). In the 3xDNA arm, 26 (37%) recipients developed a broader T-cell response (Env plus at least to one of the Gag, Pol, Nef pools) than in the 2xDNA (15; 22%) arms (primary endpoint; P = 0.047) with a higher magnitude against Env (at week 26) (P<0.001). In both groups, vaccine regimens induced HIV-specific polyfunctional CD4 and CD8 T cells and the production of Th1, Th2 and Th17/IL-21 cytokines. Antibody responses were also elicited in up to 81% of vaccines. A higher percentage of IgG responders was noted in the 2xDNA arm compared to the 3xDNA arm, while the 3xDNA group tended to elicit a higher magnitude of IgG3 response against specific Env antigens. We show here that the modulation of the prime strategy, without modifying the route or the dose of administration, or the combination of vectors, may influence the quality of the responses.
The French health authorities extended vaccination against COVID-19 to adolescents in June 2021, during the epidemic resurgence linked to the delta variant and because of insufficient vaccination ...coverage to ensure collective protection. In May 2021, we conducted a national online cross-sectional survey of 2533 adults in France to study their attitudes toward COVID-19 vaccines and their acceptance of child/adolescent vaccination according to targeted age groups (<6 years; 6-11; 12-17) and its determinants. We applied a multi-model averaged logistic regression for each of these age groups to study the determinants of favorability to vaccination. Among the respondents, 62.7% (1597) accepted COVID-19 vaccination for adolescents, 48.3% (1223) for children aged 6-11 years, and only 31% (783) for children under 6 years. Acceptance increased with fear of contracting COVID-19 and trust in institutions and decreased as the COVID-19 vaccine risk perception score increased. People favorable to vaccination in general and those sensitive to social pressure were also more often favorable to vaccinating children/adolescents than those who were not. Drivers of acceptance were ranked differently for the different age groups. Understanding these differences is essential to anticipating obstacles to vaccination of these age groups and designing appropriate information and motivational strategies to support it.
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