This study attempts to understand coronavirus disease 2019 (COVID-19) vaccine demand and hesitancy by assessing the public's vaccination intention and willingness-to-pay (WTP). Confidence in COVID-19 ...vaccines produced in China and preference for domestically-made or foreign-made vaccines was also investigated.
A nationwide cross-sectional, self-administered online survey was conducted on 1-19 May 2020. The health belief model (HBM) was used as a theoretical framework for understanding COVID-19 vaccination intent and WTP.
A total of 3,541 complete responses were received. The majority reported a probably yes intent (54.6%), followed by a definite yes intent (28.7%). The perception that vaccination decreases the chances of getting COVID-19 under the perceived benefit construct (OR = 3.14, 95% CI 2.05-4.83) and not being concerned about the efficacy of new COVID-19 vaccines under the perceived barriers construct (OR = 1.65, 95% CI 1.31-2.09) were found to have the highest significant odds of a definite intention to take the COVID-19 vaccine. The median (interquartile range IQR) of WTP for COVID-19 vaccine was CNY¥200/US$28 (IQR CNY¥100-500/USD$14-72). The highest marginal WTP for the vaccine was influenced by socio-economic factors. The majority were confident (48.7%) and completely confident (46.1%) in domestically-made COVID-19 vaccine. 64.2% reported a preference for a domestically-made over foreign-made COVID-19 vaccine.
The findings demonstrate the utility of HBM constructs in understanding COVID-19 vaccination intent and WTP. It is important to improve health promotion and reduce the barriers to COVID-19 vaccination.
Highlights • Human vaccines against three viruses employ recombinant virus-like particles (VLPs). • VLPs are excellent vaccine antigens because they faithfully mimic the native virions. • ...Post-purification reassembly of VLPs can improve antigenicity and vaccine efficacy. • Critical quality attributes of VLPs are assessed to guide vaccine production.
The emergence of numerous variants of SARS-CoV-2, the causative agent of COVID-19, has presented new challenges to the global efforts to control the COVID-19 pandemic. Here, we obtain two ...cross-neutralizing antibodies (7D6 and 6D6) that target Sarbecoviruses' receptor-binding domain (RBD) with sub-picomolar affinities and potently neutralize authentic SARS-CoV-2. Crystal structures show that both antibodies bind a cryptic site different from that recognized by existing antibodies and highly conserved across Sarbecovirus isolates. Binding of these two antibodies to the RBD clashes with the adjacent N-terminal domain and disrupts the viral spike. Both antibodies confer good resistance to mutations in the currently circulating SARS-CoV-2 variants. Thus, our results have direct relevance to public health as options for passive antibody therapeutics and even active prophylactics. They can also inform the design of pan-sarbecovirus vaccines.
Recombinant virus-like particle-based vaccines are composed of viral structural proteins and mimic authentic native viruses but are devoid of viral genetic materials. They are the active components ...in highly safe and effective vaccines for the prevention of infectious diseases. Several expression systems have been used for virus-like particle production, ranging from
to mammalian cell lines. The prokaryotic expression system, especially
, is the preferred expression host for producing vaccines for global use. Hecolin, the first licensed virus-like particle vaccine derived from
, has been demonstrated to possess good safety and high efficacy. In this review, we focus on
-derived virus-like particle based vaccines and vaccine candidates that are used for prevention (immunization against microbial pathogens) or disease treatment (directed against cancer or non-infectious diseases). The native-like spatial or higher-order structure is essential for the function of virus-like particles. Thus, the tool box for analyzing the key physicochemical, biochemical and functional attributes of purified virus-like particles will also be discussed. In summary, the
expression system has great potentials for producing a range of proteins with self-assembling properties to be used as vaccine antigens given the proper epitopes were preserved when compared to those in the native pathogens or disease-related target molecules.
Varicella caused by the primary infection of varicella-zoster virus (VZV) exerts a considerable disease burden globally. Current varicella vaccines consisting of the live-attenuated vOka strain of ...VZV are generally safe and effective. However, vOka retains full neurovirulence and can establish latency and reactivate to cause herpes zoster in vaccine recipients, raising safety concerns. Here, we rationally design a live-attenuated varicella vaccine candidate, v7D. This virus replicates like wild-type virus in MRC-5 fibroblasts and human PBMCs, the carrier for VZV dissemination, but is severely impaired for infection of human skin and neuronal cells. Meanwhile, v7D shows immunogenicity comparable to vOka both in vitro and in multiple small animal species. Finally, v7D is proven well-tolerated and immunogenic in nonhuman primates. Our preclinical data suggest that v7D is a promising candidate as a safer live varicella vaccine with reduced risk of vaccine-related complications, and could inform the design of other herpes virus vaccines.
Enzyme-linked immunosorbent assay (ELISA) is a commonly used method in analyzing biomolecular interactions. As a rapid, specific, and easy-to-operate method, ELISA has been used as a research tool as ...well as a widely adopted diagnostic method in clinical settings and for microbial testing in various industries. Inhibition ELISA is a one-site binding analysis method, which can monitor protein-protein interactions in solution as opposed to more commonly used sandwich ELISA in which the analyte capture step is required on a solid surface either through specific capture or through passive adsorption. Here, we introduce inhibition ELISA procedures, using a recombinant viral protein as an example, with emphasis on how inhibition ELISA could be used to probe subtle protein conformational changes in solution impacting protein-protein binding affinity. Inhibition ELISA is used to probe one binding site at a time for binding partners in solution with unrestricted conformation. The assay can be performed in a quantitative manner with a serially diluted analyte in solution for solution antigenicity or binding activity assessment.
Monoclonal antibody (mAb)-based therapeutics are playing an increasingly important role in the treatment or prevention of many important diseases such as cancers, autoimmune disorders, and infectious ...diseases. Multidomain mAbs are far more complex than small molecule drugs with intrinsic heterogeneities. The critical quality attributes of a given mAb, including structure, post-translational modifications, and functions at biomolecular and cellular levels, need to be defined and profiled in details during the developmental phases of a biologics. These critical quality attributes, outlined in this review, serve an important database for defining the drug properties during commercial production phase aswell as post licensure life cycle management. Specially, the molecular characterization, functional assessment, and effector function analysis of mAbs, are reviewed with respect to the critical parameters and the methods used for obtaining them. The three groups of analytical methods are three essential and integral facets making up the whole analytical package for a mAb-based drug.Such a package is critically important for thelicensure andthepost-licensure lifecyclemanagement of a therapeutic or prophylactic biologics. In addition, the basic principles on the evaluation of biosimilarmAbs were discussed briefly based on the recommendations by the World Health Organization.
Adjuvants are essential components in vaccine formulations to induce robust immunity against pathogens. The most widely used adjuvants in human vaccines are aluminum salts, that can effectively ...elicit a T helper type-2 (Th2)-biased humoral immune response for producing a high antibody titer but with a limited cellular immune response. Biocompatible calcium phosphate nanoparticles (CaP-NPs) with tunable characteristics have potentials to function as adjuvants for inducing more balanced T helper type-1 (Th1) and Th2 immune responses. Areas covered: Here we review the preparation procedures and characteristics of CaP-NPs. The process can be well-controlled and readily scaled up. Antigen loading can take place as encapsulation during the particle formation or as passive adsorption post particle formation. Different modalities of immunogens were tested with CaP-NPs as adjuvants. The possible mechanisms of the CaP-NP-based adjuvants are discussed. Expert commentary: With good adjuvant effects and safety profiles, CaP-NPs have the potentials to be a new generation vaccine adjuvant. A more in-depth understanding of the mechanisms of their adjuvanticity could facilitate the process optimization for making adjuvants with preferred characteristics. Interdisciplinary collaborations are essential for testing the biocompatible CaP-NPs in human vaccines for clinical development and eventually for use in marketed vaccines.
The capsid of human papillomavirus (HPV) spontaneously arranges into a T = 7 icosahedral particle with 72 L1 pentameric capsomeres associating via disulfide bonds between Cys175 and Cys428. Here, we ...design a capsomere-hybrid virus-like particle (chVLP) to accommodate multiple types of L1 pentamers by the reciprocal assembly of single C175A and C428A L1 mutants, either of which alone encumbers L1 pentamer particle self-assembly. We show that co-assembly between any pair of C175A and C428A mutants across at least nine HPV genotypes occurs at a preferred equal molar stoichiometry, irrespective of the type or number of L1 sequences. A nine-valent chVLP vaccine-formed through the structural clustering of HPV epitopes-confers neutralization titers that are comparable with that of Gardasil 9 and elicits minor cross-neutralizing antibodies against some heterologous HPV types. These findings may pave the way for a new vaccine design that targets multiple pathogenic variants or cancer cells bearing diverse neoantigens.
The availability of various types of COVID-19 vaccines and diverse characteristics of the vaccines present a dilemma in vaccination choices, which may result in individuals refusing a particular ...COVID-19 vaccine offered, hence presenting a threat to immunisation coverage and reaching herd immunity. The study aimed to assess global COVID-19 vaccination intention, vaccine characteristics influencing vaccination acceptance and desirable vaccine characteristics influencing the choice of vaccines.
An anonymous cross-sectional survey was conducted between 4 January and 5 March 2021 in 17 countries worldwide. Proportions and the corresponding 95% confidence intervals (CI) of COVID-19 vaccine acceptance and vaccine characteristics influencing vaccination acceptance were generated and compared across countries and regions. Multivariable logistic regression analysis was used to determine the factors associated with COVID-19 vaccine hesitancy.
Of the 19,714 responses received, 90.4% (95% CI 81.8-95.3) reported likely or extremely likely to receive COVID-19 vaccine. A high proportion of likely or extremely likely to receive the COVID-19 vaccine was reported in Australia (96.4%), China (95.3%) and Norway (95.3%), while a high proportion reported being unlikely or extremely unlikely to receive the vaccine in Japan (34.6%), the U.S. (29.4%) and Iran (27.9%). Males, those with a lower educational level and those of older age expressed a higher level of COVID-19 vaccine hesitancy. Less than two-thirds (59.7%; 95% CI 58.4-61.0) reported only being willing to accept a vaccine with an effectiveness of more than 90%, and 74.5% (95% CI 73.4-75.5) said they would accept a COVID-19 vaccine with minor adverse reactions. A total of 21.0% (95% CI 20.0-22.0) reported not accepting an mRNA vaccine and 51.8% (95% CI 50.3-53.1) reported that they would only accept a COVID-19 vaccine from a specific country-of-origin. Countries from the Southeast Asia region reported the highest proportion of not accepting mRNA technology. The highest proportion from Europe and the Americas would only accept a vaccine produced by certain countries. The foremost important vaccine characteristic influencing vaccine choice is adverse reactions (40.6%; 95% CI 39.3-41.9) of a vaccine and effectiveness threshold (35.1%; 95% CI 33.9-36.4).
The inter-regional and individual country disparities in COVID-19 vaccine hesitancy highlight the importance of designing an efficient plan for the delivery of interventions dynamically tailored to the local population.
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