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Vaccine Oct 2023The development of safe and effective second-generation COVID-19 vaccines to improve affordability and storage stability requirements remains a high priority to expand... (Comparative Study)
Comparative Study
Formulation development and comparability studies with an aluminum-salt adjuvanted SARS-CoV-2 spike ferritin nanoparticle vaccine antigen produced from two different cell lines.
The development of safe and effective second-generation COVID-19 vaccines to improve affordability and storage stability requirements remains a high priority to expand global coverage. In this report, we describe formulation development and comparability studies with a self-assembled SARS-CoV-2 spike ferritin nanoparticle vaccine antigen (called DCFHP), when produced in two different cell lines and formulated with an aluminum-salt adjuvant (Alhydrogel, AH). Varying levels of phosphate buffer altered the extent and strength of antigen-adjuvant interactions, and these formulations were evaluated for their (1) in vivo performance in mice and (2) in vitro stability profiles. Unadjuvanted DCFHP produced minimal immune responses while AH-adjuvanted formulations elicited greatly enhanced pseudovirus neutralization titers independent of ∼100%, ∼40% or ∼10% of the DCFHP antigen adsorbed to AH. These formulations differed, however, in their in vitro stability properties as determined by biophysical studies and a competitive ELISA for measuring ACE2 receptor binding of AH-bound antigen. Interestingly, after one month of 4°C storage, small increases in antigenicity with concomitant decreases in the ability to desorb the antigen from the AH were observed. Finally, we performed a comparability assessment of DCFHP antigen produced in Expi293 and CHO cells, which displayed expected differences in their N-linked oligosaccharide profiles. Despite consisting of different DCFHP glycoforms, these two preparations were highly similar in their key quality attributes including molecular size, structural integrity, conformational stability, binding to ACE2 receptor and mouse immunogenicity profiles. Taken together, these studies support future preclinical and clinical development of an AH-adjuvanted DCFHP vaccine candidate produced in CHO cells.
Topics: Animals; Spike Glycoprotein, Coronavirus; COVID-19 Vaccines; Adjuvants, Immunologic; Mice; Ferritins; SARS-CoV-2; COVID-19; Nanoparticles; Humans; Antibodies, Neutralizing; Female; Antibodies, Viral; Cell Line; Cricetulus; CHO Cells; Mice, Inbred BALB C; Aluminum Hydroxide; Immunogenicity, Vaccine; Nanovaccines
PubMed: 37620203
DOI: 10.1016/j.vaccine.2023.08.037 -
Expert Review of Vaccines 2024The mRNA vaccine technologies have progressed rapidly in recent years. The COVID-19 pandemic has accelerated the application of mRNA vaccines, with research and... (Review)
Review
INTRODUCTION
The mRNA vaccine technologies have progressed rapidly in recent years. The COVID-19 pandemic has accelerated the application of mRNA vaccines, with research and development and clinical trials underway for many vaccines. Application of the quality by design (QbD) framework to mRNA vaccine development and establishing standardized quality control protocols for mRNA vaccines are essential for the continued development of high-quality mRNA vaccines.
AREAS COVERED
mRNA vaccines include linear mRNA, self-amplifying mRNA, and circular RNA vaccines. This article summarizes the progress of research on quality control of these three types of vaccines and presents associated challenges and considerations.
EXPERT OPINION
Although there has been rapid progress in research on linear mRNA vaccines, their degradation patterns remain unclear. In addition, standardized assays for key impurities, such as residual dsRNA and T7 RNA polymerase, are still lacking. For self-amplifying mRNA vaccines, a key focus should be control of stability in vivo and in vitro. For circular RNA vaccines, standardized assays, and reference standards for determining degree of circularization should be established and optimized.
Topics: Humans; Quality Control; COVID-19 Vaccines; mRNA Vaccines; COVID-19; Vaccines, Synthetic; Vaccine Development; Animals; RNA, Messenger; SARS-CoV-2
PubMed: 38733272
DOI: 10.1080/14760584.2024.2354251 -
Frontiers in Public Health 2023Development of Robust and Innovative Vaccine Effectiveness (DRIVE) was a European public-private partnership (PPP) that aimed to provide annual, brand-specific estimates... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Development of Robust and Innovative Vaccine Effectiveness (DRIVE) was a European public-private partnership (PPP) that aimed to provide annual, brand-specific estimates of influenza vaccine effectiveness (IVE) for regulatory and public health purposes. DRIVE was launched in 2017 under the umbrella of the Innovative Medicines Initiative (IMI) and conducted IVE studies from its pilot season in 2017-2018 to its final season in 2021-2022.
METHODS
In 2021-2022, DRIVE conducted four primary care-based test-negative design (TND) studies (Austria, Italy, Iceland, and England; involving >1,000 general practitioners), nine hospital-based TND studies (France, Iceland, Italy, Romania, and Spain, for a total of 21 hospitals), and one population-based cohort study in Finland. In the TND studies, patients with influenza-like illness (primary care) or severe acute respiratory infection (hospital) were enrolled, and laboratory tested for influenza using RT-PCR. Study contributor-specific IVE was calculated using logistic regression, adjusting for age, sex, and calendar time, and pooled by meta-analysis.
RESULTS
In 2021-2022, pooled confounder-adjusted influenza vaccine effectiveness (IVE) estimates against laboratory-confirmed influenza (LCI) overall and per type and subtype/lineage was produced, albeit with wide confidence intervals (CI). The limited circulation of influenza in Europe did not allow the network to reach the optimal sample size to produce precise IVE estimates for all the brands included. The most significant IVE estimates were 76% (95% CI 23%-93%) for any vaccine and 81% (22%-95%) for Vaxigrip Tetra in adults ≥65 years old and 64% (25%-83%) for Fluenz Tetra in children (TND primary care setting), 85% (12%-97%) for any vaccine in adults 18-64 years (TND hospital setting), and 38% (1%-62%) in children 6 months-6 years (population-based cohort, mixed setting).
DISCUSSION
Over five seasons, DRIVE collected data on >35,000 patients, more than 60 variables, and 13 influenza vaccines. DRIVE demonstrated that estimating brand-specific IVE across Europe is possible, but achieving sufficient sample size to obtain precise estimates for all relevant stratifications remains a challenge. Finally, DRIVE's network of study contributors and lessons learned have greatly contributed to the development of the COVID-19 vaccine effectiveness platform COVIDRIVE.
Topics: Adult; Aged; Child; Humans; Cohort Studies; COVID-19; COVID-19 Vaccines; Europe; Influenza Vaccines; Influenza, Human; Seasons; Vaccine Efficacy; Male; Female; Adolescent; Young Adult; Middle Aged
PubMed: 37546295
DOI: 10.3389/fpubh.2023.1195409 -
Frontiers in Cellular and Infection... 2023While () bacteria are part of the human commensal flora, opportunistic invasion following breach of the epithelial layers can lead to a wide array of infection... (Review)
Review
While () bacteria are part of the human commensal flora, opportunistic invasion following breach of the epithelial layers can lead to a wide array of infection syndromes at both local and distant sites. Despite ubiquitous exposure from early infancy, the life-long risk of opportunistic infection is facilitated by a broad repertoire of virulence proteins. These proteins play a key role in inhibiting development of a long-term protective immune response by mechanisms ranging from dysregulation of the complement cascade to the disruption of leukocyte migration. In this review we describe the recent progress made in dissecting immune evasion, focusing on the role of the superantigen, staphylococcal protein A (SpA). Evasion of the normal human immune response drives the ability of to cause infection, often recurrently, and is also thought to be a major hindrance in the development of effective vaccination strategies. Understanding the role of virulence protein and determining methods overcoming or subverting these mechanisms could lead to much-needed breakthroughs in vaccine and monoclonal antibody development.
Topics: Humans; Staphylococcal Protein A; Staphylococcus aureus; Immune Evasion; Staphylococcal Infections; Vaccine Development
PubMed: 37829608
DOI: 10.3389/fcimb.2023.1242702 -
Pathogens (Basel, Switzerland) Sep 2023The genus encompasses several species of apicomplexan hemoprotozoan parasites [...].
The genus encompasses several species of apicomplexan hemoprotozoan parasites [...].
PubMed: 37764974
DOI: 10.3390/pathogens12091166 -
Diseases (Basel, Switzerland) Dec 2023The COVID-19 pandemic has had a profound impact on societies, public health, healthcare systems, and the world economy. With over 771 million people infected worldwide... (Review)
Review
The COVID-19 pandemic has had a profound impact on societies, public health, healthcare systems, and the world economy. With over 771 million people infected worldwide and a staggering death toll exceeding 6,960,783 as of 4 October 2023 (according to the World Health Organization), the urgency for a solution was paramount. Since the outbreak, the demand for immediate treatment for COVID-19 viral infection, as well as for effective vaccination against this virus, was soaring, which led scientists, pharmaceutical/biotech companies, government health agencies, etc., to think about a treatment strategy that could control and minimize this outbreak as soon as possible. Vaccination emerged as the most effective strategy to combat this infectious disease. For vaccination strategies, any conventional vaccine approach using attenuated live or inactivated/engineered virus, as well as other approaches, typically requires years of research and assessment. However, the urgency of the situation promoted a faster and more effective approach to vaccine development against COVID-19. The role of nanotechnology in designing, manufacturing, boosting, and delivering vaccines to the host to counter this virus was unquestionably valued and assessed. Several nanoformulations are discussed here in terms of their composition, physical properties, credibility, and applications in past vaccine development (as well as the possibility of using those used in previous applications for the generation of the COVID-19 vaccine). Controlling and eliminating the spread of the virus and preventing future recurrence requires a safe, tolerable, and effective vaccine strategy. In this review, we discuss the potential of nanoformulations as the basis for an effective vaccine strategy against COVID-19.
PubMed: 38131983
DOI: 10.3390/diseases11040177 -
Frontiers in Veterinary Science 2023is distributed worldwide, causing substantial economic losses in the animal husbandry industry. Human fasciolosis is an emerging zoonosis in Andean America, Asia, and... (Review)
Review
is distributed worldwide, causing substantial economic losses in the animal husbandry industry. Human fasciolosis is an emerging zoonosis in Andean America, Asia, and Africa. The control of the disease, both in humans and animals, is based on using anthelmintic drugs, which has resulted in increased resistance to the most effective anthelmintics, such as triclabendazole, in many countries. This, together with the concerns about drug residues in food and the environment, has increased the interest in preventive measures such as a vaccine to help control the disease in endemic areas. Despite important efforts over the past two decades and the work carried out with numerous vaccine candidates, none of them has demonstrated consistent and reproducible protection in target species. This is at least in part due to the high immunomodulation capacity of the parasite, making ineffective the host response in susceptible species such as ruminants. It is widely accepted that a deeper knowledge of the host-parasite interactions is needed for a more rational design of vaccine candidates. In recent years, the use of emerging technologies has notably increased the amount of data about these interactions. In the present study, current knowledge of host-parasite interactions and their implication in vaccine development is reviewed.
PubMed: 38149297
DOI: 10.3389/fvets.2023.1270064 -
The Journal of Allergy and Clinical... Nov 2023Obesity and type 2 diabetes mellitus (T2DM) are associated with an increased risk of severe outcomes from infectious diseases, including coronavirus disease 2019. These...
BACKGROUND
Obesity and type 2 diabetes mellitus (T2DM) are associated with an increased risk of severe outcomes from infectious diseases, including coronavirus disease 2019. These conditions are also associated with distinct responses to immunization, including an impaired response to widely used severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccines.
OBJECTIVE
We sought to establish a connection between reduced immunization efficacy via modeling the effects of metabolic diseases on vaccine immunogenicity that is essential for the development of more effective vaccines for this distinct vulnerable population.
METHODS
A murine model of diet-induced obesity and insulin resistance was used to model the effects of comorbid T2DM and obesity on vaccine immunogenicity and protection.
RESULTS
Mice fed a high-fat diet (HFD) developed obesity, hyperinsulinemia, and glucose intolerance. Relative to mice fed a normal diet, HFD mice vaccinated with a SARS-CoV-2 mRNA vaccine exhibited significantly lower anti-spike IgG titers, predominantly in the IgG2c subclass, associated with a lower type 1 response, along with a 3.83-fold decrease in neutralizing titers. Furthermore, enhanced vaccine-induced spike-specific CD8 T-cell activation and protection from lung infection against SARS-CoV-2 challenge were seen only in mice fed a normal diet but not in HFD mice.
CONCLUSIONS
The study demonstrated impaired immunity following SARS-CoV-2 mRNA immunization in a murine model of comorbid T2DM and obesity, supporting the need for further research into the basis for impaired anti-SARS-CoV-2 immunity in T2DM and investigation of novel approaches to enhance vaccine immunogenicity among those with metabolic diseases.
Topics: Animals; Humans; Mice; COVID-19 Vaccines; SARS-CoV-2; COVID-19; Disease Models, Animal; Viral Vaccines; Insulin Resistance; Immunogenicity, Vaccine; Diabetes Mellitus, Type 2; Diet; Obesity; RNA, Messenger; Antibodies, Viral; Antibodies, Neutralizing
PubMed: 37595760
DOI: 10.1016/j.jaci.2023.06.031 -
Antiviral Research Aug 2023Vaccination remains the best prevention strategy against influenza. The MDCK-based influenza vaccine prompted the development of innovative cell culture manufacturing...
Vaccination remains the best prevention strategy against influenza. The MDCK-based influenza vaccine prompted the development of innovative cell culture manufacturing processes. In the present study, we report the effects of multiple administrations of a candidate, seasonal, MDCK-based, quadrivalent split influenza virus vaccine MDCK-QIV in Sprague-Dawley (SD) rats. Moreover, the effects of the vaccine were evaluated in terms of fertility and early embryonic development, embryo-fetal development, and perinatal toxicity in the SD rats and immunogenicity in Wistar rats and BALB/c mice. Regarding the safety profile, MDCK-QIV demonstrated tolerance in local stimulation with repeated dose administration and presented no significant effect on the development, growth, behavior, fertility, and reproductive performance of the adult male rats, maternal rats, and their offspring. MDCK-QIV elicited strong hemagglutination inhibition neutralizing antibody response and protection against the influenza virus in the mouse model. Thus, data supported that MDCK-QIV could be further evaluated in human clinical trial, which is currently underway.
Topics: Adult; Humans; Mice; Male; Rats; Animals; Influenza Vaccines; Influenza B virus; Seasons; Antibodies, Viral; Rats, Sprague-Dawley; Rats, Wistar; Influenza, Human; Hemagglutination Inhibition Tests; Vaccines, Combined; Immunogenicity, Vaccine; Vaccines, Inactivated
PubMed: 37270159
DOI: 10.1016/j.antiviral.2023.105639 -
Nature Communications Mar 2024Disease-modifying therapies (DMT) administered to patients with multiple sclerosis (MS) can influence immune responses to SARS-CoV-2 and vaccine efficacy. However, data...
Disease-modifying therapies (DMT) administered to patients with multiple sclerosis (MS) can influence immune responses to SARS-CoV-2 and vaccine efficacy. However, data on the detailed phenotypic, functional and metabolic characteristics of antigen (Ag)-specific cells following the third dose of mRNA vaccine remain scarce. Here, using flow cytometry and 45-parameter mass cytometry, we broadly investigate the phenotype, function and the single-cell metabolic profile of SARS-CoV-2-specific T and B cells up to 8 months after the third dose of mRNA vaccine in a cohort of 94 patients with MS treated with different DMT, including cladribine, dimethyl fumarate, fingolimod, interferon, natalizumab, teriflunomide, rituximab or ocrelizumab. Almost all patients display functional immune response to SARS-CoV-2. Different metabolic profiles characterize antigen-specific-T and -B cell response in fingolimod- and natalizumab-treated patients, whose immune response differs from all the other MS treatments.
Topics: Humans; Multiple Sclerosis; Immunosuppressive Agents; Fingolimod Hydrochloride; SARS-CoV-2; Natalizumab; Vaccine Efficacy; mRNA Vaccines; COVID-19; Immunosenescence
PubMed: 38553477
DOI: 10.1038/s41467-024-47013-0