Abstract:The COVID-19 pandemic caused by SARS-CoV-2 seriously threatens global public health. It has previously been confirmed that SARS-CoV-2 is mainly transmitted between people through “respiratory droplets”. Therefore, the respiratory tract mucosa is the first barrier to prevent virus invasion. It is very important to stimulate mucosal immunity to protect the body from respiratory virus infection. Inspired by this, we designed a bionic-virus nanovaccine, which can induce mucosal immunity by nasal delivery to preven… Show more
“…It has been commonly believed that intramuscular vaccines do not induce mucosal immunity effectively (21). The mucosal immune response of the upper respiratory tract is partly compartmentalized and usually initiated in nasopharynx-associated lymphoid tissue (NALT) in all age groups and bronchus-associated lymphoid tissue (BALT) in children and adolescents or in adults upon disease induction (18).…”
Section: % Nab Detection In Coronavac Subjects' Plasmamentioning
Vaccines that elicit mucosal immune responses against SARS-CoV-2 could potentially be of exceptional importance in providing first line defense at the site of viral entry. The serological antibody response induced by SARS-CoV-2 vaccines have already been well characterized. In order to understand the mucosal immune response profiles of SARS-CoV-2 vaccines, we examined both the mucosal and systemic responses of subjects vaccinated by two different vaccination platforms: mRNA (Comirnaty) and inactivated virus (CoronaVac). Serial nasal epithelial lining fluid (NELF) and peripheral blood samples were collected in ten subjects who had received CoronaVac and thirty-two subjects who had received Comirnaty. We quantified IgA and IgG specific to SARS-CoV-2 S1 protein by ELISA in NELF and plasma samples. The neutralization effect of these two sample types were evaluated by surrogate ACE-SARS-CoV-2 Spike protein ELISA. Only Comirnaty induced nasal SARS-CoV-2 S1 protein-specific (S1-specific) IgA and IgG responses, which were evident as early as on 14 days after the first dose. The NELF samples of 72% of subjects became IgA+IgG+, while in 62.5% of subjects the samples were neutralizing by 7 days after the second dose. In 45% of the subjects their NELF remained neutralizing 50 days after the booster of Comirnaty. In plasma, 91% and 100% Comirnaty subjects possessed S1-specific IgA+IgG+ on 14 days after the first dose and 7 days after booster, respectively. The plasma collected on 7 days after booster was 100% neutralizing. The induction of S1-specific antibody by CoronaVac was IgG dominant, and 70% of the subjects possessed S1-specific IgG by 7 days after booster and were all neutralizing. This study reveals that Comirnaty is able to induce S1-specific IgA and IgG response with neutralizing activity in the nasal mucosa in addition to a consistent systemic response. The clinical implications and the biological mechanism of an additional nasal immune response induced by vaccines such as Comirnaty warrant further investigation.
“…It has been commonly believed that intramuscular vaccines do not induce mucosal immunity effectively (21). The mucosal immune response of the upper respiratory tract is partly compartmentalized and usually initiated in nasopharynx-associated lymphoid tissue (NALT) in all age groups and bronchus-associated lymphoid tissue (BALT) in children and adolescents or in adults upon disease induction (18).…”
Section: % Nab Detection In Coronavac Subjects' Plasmamentioning
Vaccines that elicit mucosal immune responses against SARS-CoV-2 could potentially be of exceptional importance in providing first line defense at the site of viral entry. The serological antibody response induced by SARS-CoV-2 vaccines have already been well characterized. In order to understand the mucosal immune response profiles of SARS-CoV-2 vaccines, we examined both the mucosal and systemic responses of subjects vaccinated by two different vaccination platforms: mRNA (Comirnaty) and inactivated virus (CoronaVac). Serial nasal epithelial lining fluid (NELF) and peripheral blood samples were collected in ten subjects who had received CoronaVac and thirty-two subjects who had received Comirnaty. We quantified IgA and IgG specific to SARS-CoV-2 S1 protein by ELISA in NELF and plasma samples. The neutralization effect of these two sample types were evaluated by surrogate ACE-SARS-CoV-2 Spike protein ELISA. Only Comirnaty induced nasal SARS-CoV-2 S1 protein-specific (S1-specific) IgA and IgG responses, which were evident as early as on 14 days after the first dose. The NELF samples of 72% of subjects became IgA+IgG+, while in 62.5% of subjects the samples were neutralizing by 7 days after the second dose. In 45% of the subjects their NELF remained neutralizing 50 days after the booster of Comirnaty. In plasma, 91% and 100% Comirnaty subjects possessed S1-specific IgA+IgG+ on 14 days after the first dose and 7 days after booster, respectively. The plasma collected on 7 days after booster was 100% neutralizing. The induction of S1-specific antibody by CoronaVac was IgG dominant, and 70% of the subjects possessed S1-specific IgG by 7 days after booster and were all neutralizing. This study reveals that Comirnaty is able to induce S1-specific IgA and IgG response with neutralizing activity in the nasal mucosa in addition to a consistent systemic response. The clinical implications and the biological mechanism of an additional nasal immune response induced by vaccines such as Comirnaty warrant further investigation.
“…Most studies use structural proteins such as the spike (S), envelope (E) or membrane (M) proteins to act as inducers of neutralizing antibodies. 46 , 49 …”
Advances in nanobiotechnology have allowed the utilization of nanotechnology through nanovaccines. Nanovaccines are powerful tools for enhancing the immunogenicity of a specific antigen and exhibit advantages over other adjuvant approaches, with features such as expanded stability, prolonged release, decreased immunotoxicity, and immunogenic selectivity. We introduce recent advances in carbon nanotubes (CNTs) to induce either a carrier effect as a nanoplatform or an immunostimulatory effect. Several studies of CNT-based nanovaccines revealed that due to the ability of CNTs to carry immunogenic molecules, they can act as nonclassical vaccines, a quality not possessed by vaccines with traditional formulations. Therefore, adapting and modifying the physicochemical properties of CNTs for use in vaccines may additionally enhance their efficacy in inducing a T cell-based immune response. Accordingly, the purpose of this study is to renew and awaken interest in and knowledge of the safe use of CNTs as adjuvants and carriers in vaccines.
“…Other approaches focus on subunit vaccines self-assembled into virus-like particles (VLPs) as reviewed in [ 41 , 87 ], bacteria-based expression of SARS-CoV-2 membrane and nucleocapsid proteins [ 88 ]. Given that the respiratory mucosa is the first main barrier for preventing SARS-CoV-2 invasion, another interesting strategy is to develop nanoparticles mimicking SARS-CoV-2 structure and activity to elicit anti-COVID-19 mucosal immunity in the respiratory tract ( Figure 3a ) [ 89 ]. Here, virosome-mimicking nano-enabled bionic vaccine was composed of synthetic double-stranded RNA poly(I:C) as immune adjuvant and simulating viral RNA, pulmonary surfactant-based liposomes mimicking viral capsid and SARS-CoV-2 receptor-binding domains (RBDs) acting as the viral spike, assembling a complex biomimetic inhalable nanovaccine sized around 154 nm (similar to SARS-CoV-2) and aimed at nasal administration ( Figure 3(b,c )).…”
Section: Introductionmentioning
confidence: 99%
“…Additionally, the nanovaccines could stimulate CD4+ T cells differentiation ( Figure 3(d-g) ), thus promoting humoral activation and enhanced secretion of neutralizing antibodies, as well as B cell activation in the spleen ( Figure 3(h,i) ). Importantly, the nanovaccine showed remarkable immune protection and mucosal immunity performance as compared to the groups subjected to intramuscular and intraperitoneal injection, including higher sIgA titers and duration of protection ( Figure 3(j-m) ) [ 89 ]. Figure 3.…”
Introduction
: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a particular coronavirus strain responsible for the coronavirus disease 2019 (COVID-19), accounting for more than 3.1 million deaths worldwide. Several health-related strategies have been successfully developed to contain the rapidly-spreading virus across the globe, toward reduction of both disease burden and infection rates. Particularly, attention has been focused on either the development of novel drugs and vaccines, or by adapting already-existing drugs for COVID-19 treatment, mobilizing huge efforts to block disease progression and to overcome the shortage of effective measures available at this point.
Areas covered
: This perspective covers the breakthrough of multifunctional biomimetic cell membrane-based nanoparticles as next-generation nanosystems for cutting-edge COVID-19 therapeutics and vaccination, specifically cell membrane-derived nanovesicles and cell membrane-coated nanoparticles, both tailorable cell membrane-based nanosystems enriched with the surface repertoire of native cell membranes, toward maximized biointerfacing, immune evasion, cell targeting and cell-mimicking properties.
Expert opinion
: Nano-based approaches have received widespread interest regarding enhanced antigen delivery, prolonged blood circulation half-life and controlled release of drugs. Cell membrane-based nanoparticles comprise interesting antiviral multifunctional nanoplatforms for blocking SARS-CoV-2 binding to host cells, reducing inflammation through cytokine neutralization and improving drug delivery toward COVID-19 treatment.
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