is the second most deadly diarrheal disease among children under five years of age, after rotavirus, with high morbidity and mortality in developing countries. Currently, no vaccine is widely ...available, and the increasing levels of multidrug resistance make
a high priority for vaccine development. The single-component candidate vaccine against
(1790GAHB), developed using the GMMA technology, contains the O antigen (OAg) portion of lipopolysaccharide (LPS) as active moiety. The vaccine was well tolerated and immunogenic in early-phase clinical trials. In a phase 1 placebo-controlled dose escalation trial in France (NCT02017899), three doses of five different vaccine formulations (0.06/1, 0.3/5, 1.5/25, 3/50, 6/100 µg of OAg/protein) were administered to healthy adults. In the phase 1 extension trial (NCT03089879), conducted 2-3 years following the parent study, primed individuals who had undetectable antibody levels before the primary series received a 1790GAHB booster dose (1.5/25 µg OAg/protein). Controls were unprimed participants immunized with one 1790GAHB dose. The current analysis assessed the functionality of sera collected from both studies using a high-throughput luminescence-based serum bactericidal activity (SBA) assay optimized for testing human sera. Antibodies with complement-mediated bactericidal activity were detected in vaccinees but not in placebo recipients. SBA titers increased with OAg dose, with a persistent response up to six months after the primary vaccination with at least 1.5/25 µg of OAg/protein. The booster dose induced a strong increase of SBA titers in most primed participants. Correlation between SBA titers and anti-
LPS serum immunoglobulin G levels was observed. Results suggest that GMMA is a promising OAg delivery system for the generation of functional antibody responses and persistent immunological memory.
In spite of the widespread implementation of preventive strategies, the prevalence of healthcare-associated infections (HAIs) remains high. HAIs are associated with multidrug resistant organisms, and ...in the post-antibiotic era, alternative strategies such as vaccines are needed for their management. Areas covered: Vaccines to prevent HAIs could be proposed to at-risk patients, or to healthcare workers (HCWs) to prevent cross-transmission. After searches in Pubmed and clinicaltrials.gov, existing vaccines and vaccines under clinical development are presented in this narrative review. Issues associated with the use of vaccines to prevent HAIs are discussed. Expert commentary: Future vaccines against HAIs will contribute to fight antibiotic resistance and thus reduce the burden of HAIs. At this stage, the goal of obtaining effective vaccines against S.aureus, C. difficile and gram-negative bacteria has not yet been achieved. Obtaining an efficient response to vaccines in at-risk patients for HAIs is also challenging, and future strategies of vaccination need to address this difficulty. The efficacy of vaccines for HCWs in reducing the spread of nosocomial outbreaks is counterbalanced by the lack of adherence to vaccine policies among HCWs. The acceptance of future vaccines to prevent carriage and infection with organisms involved in HAIs in HCWs will probably be a challenge.
The lifting of non-pharmaceutical measures preventing transmission of SARS-CoV-2 (and other viruses, including influenza viruses) raises concerns about healthcare resources and fears of an increased ...number of cases of influenza and COVID-19. For the 2021-2022 influenza season, the WHO and >20 European countries promoted coadministration of influenza and COVID-19 vaccines. Recently, the French Health Authority recommended coupling the COVID-19 vaccination with the 2022-2023 influenza vaccination campaign for healthcare professionals and people at risk of severe COVID-19. The present systematic review examines published data on the safety, immunogenicity, efficacy/effectiveness, and acceptability/acceptance of coadministration of influenza and COVID-19 vaccines. No safety concerns or immune interferences were found whatever the vaccines or the age of vaccinated subjects (65- or 65+). No efficacy/effectiveness data were available. The results should reassure vaccinees and vaccinators in case of coadministration and increase vaccine coverage. Healthcare systems promoting coupled campaigns must provide the necessary means for successful coadministration.
The lifting of non-pharmaceutical measures recommended to prevent transmission of SARS-CoV-2 (and other viruses, including influenza viruses) raises concerns about healthcare resources, already under pressure. It also raises fears of an increase in the number of cases of influenza or COVID-19 infection during the winter season. For the 2021-2022 influenza season, the World Health Organization and several European countries promoted concomitant administration in distinct anatomic sites (i.e., coadministration) of influenza and COVID-19 vaccines to avoid additional stress on healthcare systems. In May 2022, the French Health Authority recommended coupling the COVID-19 vaccination with the 2022-2023 influenza vaccination campaign (i.e., starting COVID-19 vaccination at the date of influenza vaccination) for healthcare professionals and people at risk of severe COVID-19, in case of epidemic wave. Coadministration of influenza and COVID-19 vaccines is one of the factors of success for a coupled campaign. The present systematic review examines all published data (articles or reports, clinical trials, or surveys) on the safety, immunogenicity, efficacy/effectiveness, and acceptability/acceptance of coadministration of influenza and COVID-19 vaccines. The PRISMA method was used to collect information. No safety concerns or immune interferences were found whatever the vaccines or the age of vaccinated subjects (65- or 65+). No efficacy/effectiveness data were available. Acceptability and acceptance were good but could be improved. By reassuring vaccinees and vaccinators, these results are expected to favor coadministration and ultimately increase vaccine coverage, thus offering better protection. Healthcare systems promoting coupled campaigns with coadministration must provide the necessary means for their successful implementation.
Due to a decades-long crisis of confidence in vaccination, in 2017 France extended the number of mandatory early childhood vaccines from 3 to 11.
To describe the opinions of hospital staff physicians ...(HSPs) regarding this measure, quantify the proportion who would have preferred measures based on education, and study the factors associated with the latter opinion.
Cross-sectional nationwide survey with a standardized questionnaire in 2018-2019 among HSPs in 14 French public hospitals. The factors associated with HSPs' preference for education and persuasion over mandatory vaccination were analyzed with simple and multiple Poisson regressions.
The analyses included 1,795 HSPs (participation rate of 86%). Among them, 84% considered the extension of mandatory childhood vaccination essential given the epidemiological context at the time; in a later question, 40% would have preferred education and persuasion. Multiple regressions showed that the latter tended to be younger and less trustful of sources of information about vaccination. They were more likely to think that information on the rationale behind the national vaccination policy lacked clarity and that the extension of mandatory vaccines was not essential, even in the current epidemiologic situation.
Although most HSPs agreed that the extension of mandatory childhood vaccines was essential, some were ambivalent about its coercive philosophy. Further research is necessary to better understand the reasons of this ambivalence. A fraction did not understand the French vaccination strategy well. Efforts to explain its details to HSPs and an overhaul of their initial training on vaccination are still needed.
Abstract
Background
Respiratory syncytial virus (RSV) is a common cause of respiratory tract illness and hospitalization in neonates and infants. RSV vaccination during pregnancy may protect ...offspring in their first months of life.
Methods
This randomized, observer-blind, multicenter, phase 2 study evaluated the immunogenicity and safety of an RSV candidate vaccine in healthy nonpregnant women aged 18–45 years. Four hundred participants were randomized (1:1:1:1) to receive a single intramuscular dose of vaccine containing 30 µg, 60 µg, or 120 µg of RSV fusion protein engineered to preferentially maintain a prefusion conformation (RSV-PreF vaccine) or placebo.
Results
Thirty days postvaccination, RSV-A neutralizing antibody geometric mean titers (GMTs) increased 3.75-, 4.42- and 4.36-fold; RSV-B neutralizing antibody GMTs 2.36-, 2.54- and 2.76-fold; and palivizumab competing antibody (PCA) concentrations 11.69-, 14.38- and 14.24-fold compared with baseline levels in the 30 µg, 60 µg, and 120 µg RSV-PreF groups, respectively. Antibody titers and PCA concentrations at day 30 were significantly higher with the 120 µg compared to the 30 µg RSV-PreF vaccine. All RSV-PreF vaccine formulations and the placebo had similar reactogenicity profiles. No serious adverse events were considered to be related to the RSV-PreF vaccine.
Conclusions
The 3 formulations of the investigational RSV-PreF vaccine were well-tolerated and induced RSV-A and RSV-B neutralizing antibodies and PCAs in healthy, nonpregnant women.
Clinical Trials Registration
NCT02956837.
Three formulations of an investigational maternal respiratory syncytial virus (RSV) vaccine containing 30, 60, or 120 µg of antigen were well-tolerated and elicited a rise in RSV-A and RSV-B neutralizing antibody titers as well as palivizumab-competing antibody titers in healthy nonpregnant women.
Background:
Yellow fever vaccine (YFV) is not advised for multiple sclerosis (MS) patients because of the potential risk of post-vaccine relapses.
Objective:
To assess the risk of relapsing-remitting ...multiple sclerosis (RR-MS) worsening after YFV.
Methods:
Non-interventional observational retrospective, exposed/non-exposed cohort study nested in the French national cohort including MS.
Results:
128 RR-MS were included. The 1-year annualized relapse rate (ARR) following YFV did not differ between exposed: 0.219 (0.420) and non-exposed subjects: 0.208 (0.521) (p = 0.92). Time to first relapse was not different between groups (adjusted hazard ratio (HR) = 1.33; 95% confidence interval (CI) = 0.53–3.30, p = 0.54).
Conclusion:
These results suggest that YFV does not worsen the course of RR-MS.
As the coronavirus disease 2019 (COVID-19) spreads across the world, the rapid distribution of an effective vaccine and its acceptability among the population constitute priorities for health ...authorities. This study aimed to document attitudes of the general population toward a future vaccine against COVID-19. We used the national COCONEL surveys conducted during the lockdown to identify factors associated with vaccine refusal, in the whole population, and separately among men and women. We investigate the role of socioeconomic and demographic factors as well as exposure to COVID-19. Among the 5,018 participants, 24.0% reported their intention to refuse the vaccine. Thinking this vaccine would not be safe, being against vaccination in general, and perceiving COVID-19 to be harmless were the three main reasons given to explain vaccine refusal. Women were more likely to refuse the vaccine, especially due to a reluctance toward vaccination in general or the perception that a COVID-19 vaccine would not be safe. Some factors associated with the intention to refuse the vaccine were the same among men and women such as a lack of prior vaccination against influenza, and concern over being infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), while others differed slightly according to gender such as age, and high prevalence of COVID-19 in their region of residence. Authorities should therefore guarantee that all the necessary precautions are taken before marketing the vaccine and communicate transparently on the process of its development, and on the coverage rate required to reach herd immunity.
Abbreviation: EHI: Equivalized Household Income per month; SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2.
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.
In the context of early vaccine trials aimed at evaluating the safety profile of novel vaccines, abnormal haematological values, such as neutropenia, are often reported. It is therefore important to ...evaluate how these trials should be planned not to miss potentially important safety signals, but also to understand the implications and the clinical relevance.
We report and discuss the results from five clinical trials (two with a new Shigella vaccine in the early stage of clinical development and three with licensed vaccines) where the absolute neutrophil counts (ANC) were evaluated before and after vaccination. Additionally, we have performed a systematic review of the literature on cases of neutropenia reported during vaccine trials to discuss our results in a more general context.
Both in our clinical trials and in the literature review, several cases of neutropenia have been reported, in the first two weeks after vaccination. However, neutropenia was generally transient and had a benign clinical outcome, after vaccination with either multiple novel candidates or well-known licensed vaccines. Additionally, the vaccine recipients with neutropenia frequently had lower baseline ANC than non-neutropenic vaccinees. In many instances neutropenia occurred in subjects of African descent, known to have lower ANC compared to western populations.
It is important to include ANC and other haematological tests in early vaccine trials to identify potential safety signals. Post-vaccination neutropenia is not uncommon, generally transient and clinically benign, but many vaccine trials do not have a sampling schedule that allows its detection. Given ethnic variability in the level of circulating neutrophils, normal ranges taking into account ethnicity should be used for determination of trial inclusion/exclusion criteria and classification of neutropenia related adverse events.
ClinicalTrials.gov NCT02017899, NCT02034500, NCT01771367, NCT01765413, NCT02523287.
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