Measles virus expressing the SARS-CoV-2 spike protein stabilized in its prefusion form induces higher levels of SARS-CoV-2-specific neutralizing antibodies

ANI
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Washington [US], March 13 (ANI): An attenuated measles virus expressing the SARS-CoV-2 spike protein stabilized in its prefusion form induced higher levels of SARS-CoV-2-specific neutralizing antibodies in cotton rats than a virus expressing native full-length spike protein, scientists said in research published in journal PNAS.

It also induced a robust Th1-biased T cell response in a mouse model, hamsters immunized with this virus were protected against SARS-CoV-2 infection, suggesting that it may be a safe and efficacious vaccine candidate for SARS-CoV-2.

The authors of the study were Mijia Lu, Piyush Dravid, Yuexiu Zhang, Sheetal Trivedi, Anzhong Li, Olivia Harder, Mahesh KC, among others. The findings of the research were published in the journal PNAS.

The current COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) highlights an urgent need to develop a safe, efficacious, and durable vaccine.

Using a measles virus (rMeV) vaccine strain as the backbone, we developed a series of recombinant attenuated vaccine candidates expressing various forms of the SARS-CoV-2 spike (S) protein and its receptor-binding domain (RBD) and evaluated their efficacy in cotton rat, IFNAR-/-mice, IFNAR-/--hCD46 mice, and golden Syrian hamsters.

The researchers found that rMeV expressing stabilized prefusion S protein (rMeV-preS) was more potent in inducing SARS-CoV-2-specific neutralizing antibodies than rMeV expressing full-length S protein (rMeV-S), while the rMeVs expressing different lengths of RBD (rMeV-RBD) were the least potent.

Animals immunized with rMeV-preS produced higher levels of neutralizing antibody than found in convalescent sera from COVID-19 patients and a strong Th1-biased T cell response.

The rMeV-preS also provided complete protection of hamsters from challenge with SARS-CoV-2, preventing replication in lungs and nasal turbinates, bodyweight loss, cytokine storm, and lung pathology. These data demonstrated that rMeV-preS is a safe and highly efficacious vaccine candidate, supporting its further development as a SARS-CoV-2 vaccine.

In December 2019, a novel coronavirus disease (COVID-19) was first identified in Wuhan City, Hubei Province, People's Republic of China. The causative agent was named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Globally, more than 300 SARS-CoV-2 vaccine candidates are in preclinical development and at least 30 vaccine candidates have entered human clinical trials. Among them, vaccines based on messenger RNA (mRNA), inactivated virus, and adenovirus vectors (Ad5-nCoV and ChAdOx1) are now in phase III clinical trials.

Excitingly, preliminary results indicate that these vaccines are highly efficacious, reaching 90 to 95 per cent effectiveness against SARS-CoV-2 infection in some cases. The durability of the protection conferred by these vaccine candidates is unknown. Although these vaccine candidates are highly promising, exploration of other vaccine platforms is needed.

Live attenuated measles virus (MeV) vaccine has been one of the safest and most efficient human vaccines and has been used in children since the 1960s. Worldwide MeV vaccination campaigns have been very successful in controlling measles.

MeV is an enveloped nonsegmented negative-sense RNA virus that belongs to the genus Morbillivirus within the Paramyxoviridae family. MeV is an excellent vector to deliver vaccines for human pathogens primarily because of its high safety, efficacy, and long-lived immunity.

MeV has previously been shown to be a highly efficacious vaccine vector for many viral diseases such as HIV, SARS-CoV-1, MERS-CoV, respiratory syncytial virus, hepatitis B and C viruses, influenza virus, chikungunya virus, and flaviviruses. Recent human clinical trials have demonstrated that a recombinant MeV (rMeV)-based CHIKV vaccine is safe and highly immunogenic in healthy adults, even in the presence of preexisting anti-MeV vector immunity.

In this study, the researchers developed a series of rMeV-based vaccine candidates expressing different forms of the SARS-CoV-2 S protein and evaluated them in cotton rats, IFNAR-/-mice, IFNAR-/--hCD46 mice, and golden Syrian hamsters.

They found that all SARS-CoV-2 S antigens are highly expressed by the MeV vector. Among these vaccine candidates, rMeV expressing stabilized preS (rMeV-preS) and full-length S (rMeV-S) proteins were the most potent in triggering SARS-CoV-2-specific antibodies.

Animals immunized with rMeV-preS induced the highest level of neutralizing antibodies that were higher than convalescent sera of patients recovered from COVID-19, and the highest Th1-biased T cell immune response. Furthermore, hamsters immunized with rMeV-preS provided complete protection against SARS-CoV-2 challenge and lung pathology.

The results of the study concluded that a safe and highly efficacious rMeV-based preS vaccine candidate can provide complete protection against severe SARS-CoV-2 infection and lung pathology in animal models, supporting its further development as a vaccine. (ANI)