Prototype 2 Product Code 16

to evaluate mrna-1273-mediated protection against sars-cov-2 at the mucosal surfaces of the lung, nasal turbinates, and intestine, mice were challenged with 5×104 pfu of ma sars-cov-2 intranasally. one day post-challenge, mice were treated with three 1g doses of mrna-1273 delivered by intramuscular injection in the deltoid or pbs. tissues were collected two days post-boost, fixed, stained, and the relative infiltration of immune cells in bronchoalveolar lavage fluid (balf) of the lungs, nasal turbinates, or intestines were determined. data from the mrna-1273-treated groups were expressed as a percentage of the total number of immune cells, which was defined as the total number of leukocytes in balf minus the total number of epithelial cells in balf. balf was collected by lavaging the lungs 3 times with 1 ml of pbs. for all experiments, data were compiled and analyzed from two independent experiments.

the ability of mrna-1273 to induce protective b cell and t cell responses was assessed. serum samples were collected at 5 and 13 days post-challenge, and total anti-sars-cov-2 ncov antibody titers were quantified in 10-fold dilutions by elisa as previously described^{33, 34}. sars-cov-2-specific b and t cell responses were evaluated after immunization. mice were immunized with mrna-1273, 10g, 0.1g, or 0.01g, or pbs (mock) and splenocytes were collected 2 weeks after immunization. splenocytes were stimulated in vitro with sars-cov-2 s(2p) peptide pools. il-4 and ifn-γ cytokine production was measured by elisa after stimulation for 48h.

this is an electrical grid building (only useful for ) – this shows the pf in front of building being always lower than the 2 other building because of the high penetration of the wind turbine, although not having any effect on the heating or cooling consumption. in the left building there is no wind farm, instead the wpt is the different on the right top. the pf value for this top is therefore zero.

we developed two covid-19 vaccines and determined their protective efficacies against different challenge strains in animal models. our covid-19 vaccines were recombinant forms of full-length rbd (recombinant full-length rbd or rfrbd) produced as fusion proteins with a c-terminal his-tag or a c-terminal v5-tag. nucleocapsid (n) protein of the virus is an important structural protein that confers virus stability. the first vaccine was constructed by fusing rfrbd with n protein (rrbd-n). the second vaccine was constructed by fusing rfrbd with n and e proteins (rrbd-ne). both vaccines induced broadly reactive antibodies in rabbits and protected animals from homologous sars-cov-2 infection with titers higher than 2.5log. antibodies induced by either vaccine could bind recombinant full-length sars-cov-2 rbd (rfrbd) and inhibit its binding to ace2 (chinese hamster ovary cell line) cell surface receptors. both vaccines also cross-neutralized sars-cov-2 strains isolated from different animal species and geographical regions. rfrbd-n induced antibodies that preferentially bound to recombinant rbd (rrbd) from beta and delta sars-cov-2 variants. the antibodies induced by rrbd-ne bound to rrbd from delta and omicron variants, as well as to rfrbd from all tested variants. the immunogenicity and protective efficacies of these vaccines were not affected by virus inactivation. both vaccine candidates resulted in production of robust serum neutralizing antibodies in rabbits and two macaques, and in both species and in both expression platforms, n protein promoted generation of more potent neutralizing antibodies than rfrbd. in conclusion, rfrbd-n and rfrbd-ne vaccination induced both neutralizing and non-neutralizing antibodies and protected animals from challenge with homologous virus. anti-rbd antibodies induced by each vaccine were broadly reactive, could bind to the recombinant rbd and rbd expressed on the surface of living virus, and were protective in different animal models.
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