Collectively, these results demonstrate that this RBD trimer mRNA vaccine serves as a promising vaccine candidate against SARS-CoV-2 variants and past

jamha February 16, 2025 0 Comments

Collectively, these results demonstrate that this RBD trimer mRNA vaccine serves as a promising vaccine candidate against SARS-CoV-2 variants and past. Subject areas: Health sciences, Virology, Immunology Graphical abstract Open in a separate window Highlights ? A mRNA vaccine encoding the RBD trimer of wild-type SARS-CoV-2 was designed and studied ? The vaccine elicited strong RBD-specific memory and plasma B cell responses ? The vaccine induced broadly serum and monoclonal neutralizing antibodies in mice ? The vaccine induced strong and protective immunity against major SARS-CoV-2 variants Health sciences; Virology; Immunology Introduction The current vaccines that were developed by targeting the prototype SARS-CoV-2 strain identified during the early phase of the pandemic exhibited reduced serum cGMP Dependent Kinase Inhibitor Peptid neutralizing activity and attenuated protection against SARS-CoV-2 variants in humans (Abdool Karim and de Oliveira, 2021; Chen et?al., 2021; Corti et?al., 2021; Garcia-Beltran et?al., 2021; Harvey et?al., 2021; Madhi et?al., 2021; Planas et?al., 2021; Wang et?al., 2021a; Wang et?al., 2021b; Wang et?al., 2021c; Wibmer et?al., 2021; Zhou et?al., 2021). model of SARS-CoV-2 contamination. The protectivity was correlated with RBD-specific B cell responses especially the long-lived plasma B cells in bone marrow, strong ability in triggering BCR clustering, and downstream signaling. Monoclonal antibodies isolated from vaccinated animals exhibited broad and potent neutralizing activity against VOCs tested. Structure analysis of one representative antibody recognized a novel epitope with a high degree of conservation among different variants. Collectively, these results demonstrate that this RBD trimer mRNA vaccine serves as a encouraging vaccine candidate against SARS-CoV-2 variants and beyond. cGMP Dependent Kinase Inhibitor Peptid Subject areas: Health sciences, Virology, Immunology Graphical abstract Open in a separate window Highlights ? A mRNA vaccine encoding the RBD trimer of wild-type SARS-CoV-2 was designed and analyzed ? The vaccine elicited strong RBD-specific memory and plasma B cell responses ? The vaccine induced broadly serum and monoclonal neutralizing antibodies in mice ? The vaccine induced strong and protective immunity against major SARS-CoV-2 variants Health sciences; Virology; Immunology Introduction The current vaccines that were developed by targeting the prototype SARS-CoV-2 strain identified during the early phase of the pandemic exhibited reduced serum neutralizing activity and attenuated protection against SARS-CoV-2 variants in humans (Abdool Karim and de Oliveira, 2021; Chen et?al., 2021; Corti et?al., 2021; Garcia-Beltran et?al., 2021; Harvey et?al., 2021; Madhi et?al., 2021; Planas et?al., 2021; Wang et?al., 2021a; Wang et?al., 2021b; Wang et?al., 2021c; Wibmer et?al., 2021; Zhou et?al., 2021). While these vaccines have been designed and formulated in various modalities, they share one common feature in that they mimic and preserve the native pre-fusion conformation of the spike protein, thus are expected to induce the most relevant and effective immune response against SARS-CoV-2 (Dai and Gao, 2021; Wrapp et?al., 2020). The incredible levels of security and efficacy exhibited by these vaccines in clinical trials and ongoing vaccine rollout clearly support this shared overall strategy. However, such commonality also predisposes the vaccines to comparable escape mechanisms when it comes to SARS-CoV-2 variants. For example, the reduced level of protection provided against these variants is largely attributed to deletions in the N3 and N5 loops that collectively make up the so-called antigenic supersite in the N-terminal domain name (NTD) and the constellation of substitutions in the receptor-binding domain name, such as K417N/T, L452R, E484K/Q, and N501Y (Barnes et?al., 2020; Chen et?al., 2021; Chi et?al., 2020; Corti et?al., 2021; Garcia-Beltran et?al., 2021; Harvey et?al., 2021; McCallum et?al., 2021; Planas et?al., 2021; Suryadevara et?al., 2021; Wang et?al., 2021a, 2021b, 2021c; Wibmer et?al., 2021; Zhou et?al., 2021). Many of these mutations are shared by the B.1.1.7 variant (alpha) that was initially identified in the United Kingdom, the B.1.351 variant (beta) in South Africa, the P1 variant (gamma) in Brazil, and the B.1.617 variant (delta) in India (Abdool Karim and de Oliveira, 2021; Harvey et?al., 2021). Fortunately, by screening hundreds and thousands of monoclonal antibodies from convalescent or vaccinated individuals, a small number of broad and potent neutralizing antibodies directed to RBD were identified capable of neutralizing all variants identified thus far (Corti et?al., 2021; Harvey et?al., 2021; Tortorici et?al., 2020; Wang et?al., 2021b, 2021c). These neutralizing antibodies target numerous spatially distributed epitopes on RBD and may contribute to the residual serum neutralizing activity against SARS-CoV-2 variants of concern in these individuals (Chen et?al., 2021; Planas et?al., 2021; Wang et?al., 2021c; Wibmer et?al., 2021; Zhou et?al., 2021). More importantly, these neutralizing antibodies can be substantially boosted by mRNA vaccines, particularly in convalescent individuals (Stamatatos et?al., 2021; Wang et?al., 2021c). cGMP Dependent Kinase Inhibitor Peptid In contrast, antibodies to regions beyond the RBD, such as the NTD and S2, are inherently poor or completely lose their neutralization to SARS-CoV-2 variants Rabbit polyclonal to GAD65 (Corti et?al., 2021; Harvey et?al., 2021; Liu et?al., 2020; McCallum et?al., 2021; Robbiani et?al., 2020; Rogers et?al., 2020; Suryadevara et?al., 2021; Zhou et?al., 2021; Zost et?al., 2020). These results suggest the presence of highly conserved and vulnerable regions within the RBD that could be precisely targeted for the development of next-generation vaccines capable of inducing broad and protective immunity against SARS-CoV-2 variants. Results The development of an RBD trimer mRNA vaccine to.