Project description:Viral variants of concern may emerge with dangerous resistance to the immunity generated by the current vaccines to prevent coronavirus disease 2019 (Covid-19). Moreover, if some variants of concern have increased transmissibility or virulence, the importance of efficient public health measures and vaccination programs will increase. The global response must be both timely and science based.
Project description:The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected billions of individuals and is the cause of the current global coronavirus disease 2019 (COVID-19) pandemic. We previously developed an mRNA vaccine (LVRNA009) based on the S protein of the Wuhan-Hu-1 strain; the phases I and II clinical trials showed that LVRNA009 has a promising safety and immunogenicity profile. In order to counteract the immune escape by SARS-CoV-2 variants of concern, a panel of mRNA vaccines was developed based on the S proteins of the Wuhan-Hu-1, Delta, Omicron BA.1, BA.2, and BA.5 strains, and each vaccine’s protective potency against the virus variants was evaluated. Furthermore, to achieve excellent neutralization against SARS-CoV-2 variants, bivalent vaccines were developed and tested against the variants. We found that the monovalent Wuhan-Hu-1 or the Delta vaccines could induce high level of neutralization antibody and protect animals from the infection of the SARS-CoV-2 Wuhan-Hu-1 or Delta strains, respectively. However, serum samples from mice immunized with monovalent Delta vaccine showed relatively low virus neutralization titers (VNTs) against the pseudotyped virus of the Omicron strains. Serum samples from mice immunized with bivalent Delta/BA.1 vaccine had high VNTs against the pseudotyped Wuhan-Hu-1, Delta, and BA.1 strains but low VNTs against BA.2 and BA.5 (p < 0.05). Serum samples from mice immunized with Delta/BA.2 vaccine had high VNTs against the pseudotyped Wuhan-Hu-1, Delta, BA.1 and BA.2 strains but low VNTs against BA.5. Finally, serum samples from mice immunized with Delta/BA.5 vaccine had high VNTs against all the tested pseudotyped SARS-CoV-2 strains including the Wuhan-Hu-1, Delta, and Omicron variants (p > 0.05). Therefore, a bivalent mRNA vaccine with Delta/BA.5 combination is promising to provide broad spectrum immunity against all VOCs.
Project description:As the emerging variants of SARS-CoV-2 continue to drive the worldwide pandemic, there is a constant demand for vaccines that offer more effective and broad-spectrum protection. Here, we report a circular RNA (circRNA) vaccine that elicited potent neutralizing antibodies and T cell responses by expressing the trimeric RBD of the spike protein, providing robust protection against SARS-CoV-2 in both mice and rhesus macaques. Notably, the circRNA vaccine enabled higher and more durable antigen production than the 1mΨ-modified mRNA vaccine and elicited a higher proportion of neutralizing antibodies and distinct Th1-skewed immune responses. Importantly, we found that the circRNARBD-Omicron vaccine induced effective neutralizing antibodies against the Omicron but not the Delta variant. In contrast, the circRNARBD-Delta vaccine protected against both Delta and Omicron or functioned as a booster after two doses of either native- or Delta-specific vaccination, making it a favorable choice against the current variants of concern (VOCs) of SARS-CoV-2.
Project description:The emergence of SARS-CoV-2 variants may cause resistance at the immunity level against current vaccines. Some emergent new variants have increased transmissibility, infectivity, hospitalization, and mortality. Since the administration of the first SARS-CoV-2 vaccine to a human in March 2020, there is an ongoing global race against SARS-CoV-2 to control the current pandemic situation. Spike (S) glycoprotein of SARS-CoV-2 is the main target for current vaccine development, which can neutralize the infection. Companies and academic institutions have developed vaccines based on the S glycoprotein, as well as its antigenic domains and epitopes, which have been proven effective in generating neutralizing antibodies. The effectiveness of SARS-CoV-2 vaccines and other therapeutics developments are limited by the new emergent variants at the global level. We have discussed the emergent variants of SARS-CoV-2 on the efficacy of developed vaccines. Presently, most of the vaccines have been tremendously effective in severe diseases. However, there are still noteworthy challenges in certifying impartial vaccines; the stories of re-infections are generating more stressful conditions, and this needs further clinical evaluation.
Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of the coronavirus disease 2019 (COVID-19) pandemic, which has been a topic of major concern for global human health. The challenge to restrain the COVID-19 pandemic is further compounded by the emergence of several SARS-CoV-2 variants viz. B.1.1.7 (Alpha), B.1.351 (Beta), P1 (Gamma) and B.1.617.2 (Delta), which show increased transmissibility and resistance towards vaccines and therapies. Importantly, there is convincing evidence of increased susceptibility to SARS-CoV-2 infection among individuals with dysregulated immune response and comorbidities. Herein, we provide a comprehensive perspective regarding vulnerability of SARS-CoV-2 infection in patients with underlying medical comorbidities. We discuss ongoing vaccine (mRNA, protein-based, viral vector-based, etc.) and therapeutic (monoclonal antibodies, small molecules, plasma therapy, etc.) modalities designed to curb the COVID-19 pandemic. We also discuss in detail, the challenges posed by different SARS-CoV-2 variants of concern (VOC) identified across the globe and their effects on therapeutic and prophylactic interventions.
Project description:Over the past two years, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused hundreds of millions of infections, resulting in an unprecedented pandemic of coronavirus disease 2019 (COVID-19). As the virus spreads through the population, ongoing mutations and adaptations are being discovered. There is now substantial clinical evidence that demonstrates the SARS-CoV-2 variants have stronger transmissibility and higher virulence compared to the wild-type strain of SARS-CoV-2. Hence, development of vaccines against SARS-CoV-2 variants to boost individual immunity has become essential. However, current treatment options are limited for COVID-19 caused by the SARS-CoV-2 variants. In this review, we describe current distribution, variation, biology, and clinical features of COVID-19 caused by SARS-CoV-2 variants (including Alpha (B.1.1.7 Lineage) variant, Beta (B.1.351 Lineage) variant, Gamma (P.1 Lineage) variant, Delta (B.1.617.2 Lineage) variant, and Omicron (B.1.1.529 Lineage) variant and others. In addition, we review currently employed vaccines in clinical or preclinical phases as well as potential targeted therapies in an attempt to provide better preventive and treatment strategies for COVID-19 caused by different SARS-CoV-2 variants.