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J Infect Dis ; 2022 Apr 22.
Article in English | MEDLINE | ID: covidwho-1886443


SARS-CoV-2 Variants of Concern (VoCs) negatively impact the effectiveness of vaccines. In this study, we challenge hamsters with the Delta variant after two- or three-dose inoculations with SARS-CoV-2 vaccines constructed from stabilized prefusion spike proteins (S-2P) of Wuhan (W) and Beta (B) variants. Compared to three doses of W S-2P, two doses of W S-2P followed by a third dose of B S-2P induced the highest neutralizing antibody titer against live SARS-CoV-2 virus and enhanced neutralization of Omicron variant pseudovirus. Reduced lung live virus titer and pathology suggested that all vaccination regimens protect hamsters from SARS-CoV-2 Delta variant challenge.

Clin Infect Dis ; 74(11): 1899-1905, 2022 06 10.
Article in English | MEDLINE | ID: covidwho-1504298


BACKGROUND: Variants of concern (VoCs) have the potential to diminish the neutralizing capacity of antibodies elicited by vaccines. MVC-COV1901 is a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine consisting of recombinant prefusion stabilized spike protein S-2P adjuvanted with CpG 1018 and aluminum hydroxide. We explored the effectiveness of MVC-COV1901 against the VoCs. METHODS: Serum samples were taken from rats and phase 1 clinical trial human subjects immunized with a low, medium, or high dose of MVC-COV1901. The neutralizing titers of serum antibodies were assayed with pseudoviruses coated with the SARS-CoV-2 spike protein of the wild-type (WT), D614G, Alpha, or Beta variants. RESULTS: Rats vaccinated twice with vaccine containing high doses of antigen retained high levels of neutralization activity against the Beta variant, albeit with a slight reduction compared to WT. After the third dose, neutralizing titers against the Beta variant were noticeably enhanced regardless of the amount of antigen used for immunization. In humans, vaccinated phase 1 subjects still showed appreciable neutralization abilities against the D614G, Alpha, and Beta variants, although neutralizing titers were significantly reduced against the Beta variant. CONCLUSIONS: Two doses of MVC-COV1901 were able to elicit neutralizing antibodies against SARS-CoV-2 variants with an overall tendency of inducing higher immune response at a higher dose level. The neutralizing titers to the Beta variant in rats and humans were lower than those for WT and the Alpha variant. An additional third dose in rats was able to partially compensate for the reduction in neutralization against the Beta variant. We have demonstrated that immunization with MVC-COV1901 was effective against VoCs.

COVID-19 , SARS-CoV-2 , Adjuvants, Immunologic , Animals , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , Humans , Rats , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus , Vaccines, Subunit , Viral Envelope Proteins
Sci Rep ; 10(1): 20085, 2020 11 18.
Article in English | MEDLINE | ID: covidwho-933722


The COVID-19 pandemic is a worldwide health emergency which calls for an unprecedented race for vaccines and treatment. In developing a COVID-19 vaccine, we applied technology previously used for MERS-CoV to produce a prefusion-stabilized SARS-CoV-2 spike protein, S-2P. To enhance immunogenicity and mitigate the potential vaccine-induced immunopathology, CpG 1018, a Th1-biasing synthetic toll-like receptor 9 (TLR9) agonist was selected as an adjuvant candidate. S-2P in combination with CpG 1018 and aluminum hydroxide (alum) was found to be the most potent immunogen and induced high titer of neutralizing antibodies in sera of immunized mice against pseudotyped lentivirus reporter or live wild-type SARS-CoV-2. In addition, the antibodies elicited were able to cross-neutralize pseudovirus containing the spike protein of the D614G variant, indicating the potential for broad spectrum protection. A marked Th1 dominant response was noted from cytokines secreted by splenocytes of mice immunized with CpG 1018 and alum. No vaccine-related serious adverse effects were found in the dose-ranging study in rats administered single- or two-dose regimens of S-2P combined with CpG 1018 alone or CpG 1018 with alum. These data support continued development of CHO-derived S-2P formulated with CpG 1018 and alum as a candidate vaccine to prevent COVID-19 disease.

COVID-19 Vaccines/immunology , Immunogenicity, Vaccine , Spike Glycoprotein, Coronavirus/immunology , Adjuvants, Immunologic/therapeutic use , Aluminum Hydroxide/therapeutic use , Animals , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , CHO Cells , COVID-19 Vaccines/adverse effects , COVID-19 Vaccines/therapeutic use , Cricetinae , Cricetulus , Cytokines/blood , Cytokines/metabolism , Female , HEK293 Cells , Humans , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Oligodeoxyribonucleotides/therapeutic use , Rats , Rats, Sprague-Dawley , Spleen/immunology , Th1 Cells/immunology