ChAd vaccine against Covid-19

ChAd vaccine against Covid-19

ChAd vaccine protects upper and lower respiratory tracts against SARS-CoV-2 (Covid-19)

Chimpanzee adenovirus vectors

Article Showed the researcher used ChAd vector as vaccine platforms for SARS-CoV-2. ChAd-SARS-CoV-2-S encodes for SARS CoV-2 S protein with the two indicated proline mutations. Single dose immunization of a stabilized S protein-based vaccine via an intramuscular route induced S- and RBD-specific binding as well as neutralizing antibodies. Vaccination with one or two doses protected mice expressing human ACE2 against SARS-CoV-2 challenge, as evidenced by an absence of infectious virus in the lungs and substantially reduced viral RNA levels in lungs and other organs.

Immunization with ChAd-SARS-CoV-2-S induces both neutralizing antibody and antigen-specific CD8+ T cell responses. While a single intramuscular immunization of ChAd-SARS-CoV-2-S confers protection against SARS-CoV-2 infection and inflammation in the lungs, intranasal delivery of the vaccine induces mucosal immunity, provides superior protection, and possibly promotes sterilizing immunity, at least in mice that transiently or stably express the hACE2 receptor. Image credit: Hassan et al, doi: 10.1016/j.cell.2020.08.026.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a positive-sense single-stranded RNA virus that was first isolated in late 2019 from patients with severe respiratory illness in Wuhan, China. SARS-CoV-2 is related to two other highly pathogenic respiratory viruses, SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). SARS-CoV-2 infection results in a clinical syndrome, Coronavirus Disease 2019 (COVID-19) that can progress to respiratory failure and also present with cardiac pathology, gastrointestinal disease, coagulopathy, and a hyperinflammatory syndrome.

    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)    

        The SARS-CoV-2 RNA genome is approximately 30,000 nucleotides in length. The 5’ two-thirds encode nonstructural proteins that enable genome replication and viral RNA synthesis. The remaining one-third encode structural proteins such as spike (S), envelope, membrane, and nucleoprotein (NP) that form the spherical virion, and accessory proteins that regulate cellular responses. The S protein forms homotrimeric spikes on the virion and engages the cell-surface receptor angiotensin-converting enzyme 2 (ACE2) to promote coronavirus entry into human cells.

        The SARS-CoV and SARS-CoV-2 S proteins are cleaved sequentially during the entry process to yield S1 and S2 fragments, followed by further processing of S2 to yield a smaller S2' protein. The S1 protein includes the receptor binding domain (RBD) and the S2 protein promotes membrane fusion.This form of the S protein is recognized by potently neutralizing monoclonal antibodies and could serve as a promising vaccine target. Single intranasal dose of ChAd-SARS-CoV-2-S induced high levels of neutralizing antibody and anti-SARS-CoV-2 IgA, and conferred virtually complete protection against infection in both the upper and lower respiratory tracts in mice expressing hACE2 receptor after adenoviral vector delivery or as a trans gene. It has the potential to control infection at the site of inoculation, which should prevent both virus-induced disease and transmission.

Immunogenicity of ChAd-SARS-CoV-2-S, groups of 4-week-old BALB/c mice were immunized by intramuscular inoculation with 10¹⁰ virus particles of ChAd-SARS-CoV 2-S or ChAd-control. Some mice received a booster dose four weeks later. Serum samples were collected 21 days after primary or booster immunization, and IgG responses against purified S and RBD proteins were evaluated by ELISA. Whereas ChAd-SARS-CoV-2-S induced high levels of S- and RBD-specific IgG, low levels were detected in the ChAd control-immunized mice.

Vaccine-induced memory CD8+ T cell and antigen specific B cell responses.

Intramuscular immunization with ChAd-SARS-CoV-2-S vaccine protects against               SARS- CoV-2 infection in the lung.

A single intranasal immunization with ChAd-SARS-CoV-2-S prevents SARS-CoV-2 infection in the upper and lower respiratory tracts of hACE2 transgenic mice. Recently established a more stringent, lethal SARS-CoV-2 challenge model in transgenic C57BL/6 mice that have eight inserted copies of the hACE2 gene driven by the K18 cytokeratin epithelial cell promoter. Within one week of SARS-CoV-2 inoculation by an intranasal route, K18- hACE2 mice develop severe lung infection and inflammation, immune cell infiltration, and compromised respiratory function that results in death. As an independent test of the efficacy of intranasal administration of ChAd-SARS-CoV-2-S, Researcher assessed its immunogenicity and protective efficacy in K18-hACE2 mice. Four-week old K18-hACE2 mice were inoculated via an intranasal route with 10¹⁰ viral particles of ChAd-control or ChAd-SARS-CoV-2-S. Serum samples were collected at four weeks post-immunization and humoral immune responses were evaluated. Intranasal immunization of ChAd-SARS-CoV-2-S but not ChAd-control induced high levels of S- and RBD specific IgG and IgA and neutralizing antibodies (GMT of 1/1,424) in serum. At day 30 post-vaccination, K18-hACE2 mice were challenged via an intranasal route with 10³ FFU of SARS-CoV-2. At 4 dpi, lungs, spleen, heart, nasal turbinates, and nasal washes were harvested and assessed for viral burden. Similar to that seen in BALB/c mice transiently expressing hACE2, intranasal immunization of ChAd-SARS-CoV-2-S conferred remarkable protection as judged by an absence of infectious virus in the lungs, no measurable viral  subgenomic/genomic RNA in the lungs or hearts, and very low levels of viral RNA in the nasal  turbinates or washes. Consistent with these results, after SARS-CoV-2 challenge, observed no induction of cytokine and chemokine mRNA (e.g., CCL2, CXCL1, CXCL10, 297 CXCL11, IL6, IFNβ, and IFNλ) in the lung homogenates of ChAd-SARS-CoV-2-S-immunized  compared to naïve mice, whereas ChAd-control vaccinated mice sustained high levels . Collectively, these data suggest that a single intranasal immunization of ChAd-SARS-CoV-2-S induces robust systemic and mucosal immunity that blocks SARS-CoV-2 infection in the upper and lower respiratory tract of highly susceptible K18-hACE2 transgenic mice, source from article.

Reference

A.O. Hassan et al. 2020. A single-dose intranasal ChAd vaccine protects upper and lower respiratory tracts against SARS-CoV-2. Cell, in press; doi: 10.1016/j.cell.2020.08.026