A new synthetic multiantigen MVA COH04S1 vaccine effective against SARS-CoV-2


Scientists believe that vaccinating the entire world’s population is the key to containing the current 2019 coronavirus disease (COVID-19) pandemic. This pandemic is caused by the rapid onset of a ribonucleic acid (RNA) virus known as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).

Study: The synthetic multiantigen MVA COH04S1 vaccine protects against SARS-CoV-2 in Syrian hamsters and non-human primates. Image Credit: peterschrieber.media/Shutterstock.com

Immune protection against SARS-CoV-2

To date, several COVID-19 vaccines have received Emergency Use Authorization (EUA) from regulatory agencies in many countries around the world. Some of the vaccines that have received EUA are based on adenoviral vectors, messenger ribonucleic acid (mRNA) and nanoparticle technologies. These vaccines target different antigenic forms of the SARS-CoV-2 spike (S) protein to trigger an immune response against SARS-CoV-2.

While COVID-19 vaccines have given hope of containing the pandemic, the emergence of SARS-CoV-2 variants has extended the timeline. Indeed, certain variants of SARS-CoV-2 can escape immune responses induced by vaccines or by previous natural infections.

The decrease in neutralizing antibodies (NAb) produced by vaccines has also called into question the durability of vaccine protection. Therefore, a need exists for an alternative vaccine based on various modifications of epitopes or antigen design to provide long-lasting and long-lasting protection against variants of concern of SARS-CoV-2 (VoC).

The main immune correlate of protection includes the blockade of the S protein-angiotensin converting enzyme receptor 2 (ACE2) interaction by NAb. However, several studies have indicated that humoral and cellular immune responses are elicited by many antigens in addition to the S protein.

For example, the core (N) protein is considered a dominant target for inducing antibody production and triggering T cell responses. As the N protein is associated with a highly conserved region, it represents a favorable antigenic target. to generate long-lasting and largely reactive T cells. Numerous studies using animal models have indicated the benefits of using the N protein as the primary vaccine antigen.

The development of a multiantigenic SARS-CoV-2 vaccine using synthetic platforms

Previously, scientists had developed multiantigenic vaccine agents against SARS-CoV-2 using synthetic platforms. The Modified Vaccinia Ankara (MVA) vector, which is known as the backbone of vector vaccines, is marketed in the United States as Jynneos â„¢ (Bavarian-Nordic).

MVA is a highly attenuated poxvirus vector which is commonly used for the production of infectious disease and cancer vaccines. MVA shows many promising characteristics such as its safety profile in animals and humans, flexible delivery, and its ability to elicit potent humoral and cellular immune responses to heterologous antigens.

A new study published on the bioRxiv* The preprint server used MVA to develop candidate vaccines which were then evaluated in animal models of congenital cytomegalovirus disease. This study indicated the effectiveness of the vaccine in patients with solid tumors or those who had undergone stem cell transplants.

In this study, researchers used a synthetic MVA platform (sMVA) to develop sMVA vectors co-expressing full-length S and N antigen sequences. These sequences showed promising immunogenicity in mice, as evidenced by their ability to elicit humoral and cellular immune responses specific to the SARS-CoV-2 antigen with a high concentration of NAb.

One of the sMVA constructs is COH04S1 and is known to be a clinical vaccine candidate. In a randomized, double-blind, single-center, placebo-controlled Phase I clinical trial in healthy adults, researchers found COH04S1 to be safe and immunogenic. The present study evaluated COH04S1 in a randomized, double-blind, single-center phase II trial in hematologic patients who had previously received cell therapy.

In their study, the researchers found that COH04S1 stimulated an immune response against SARS-CoV-2 in Syrian hamsters via intramuscular (IM) and intranasal (IN) vaccination. In addition, non-human primates (PNH) have been treated with single-dose (1D) and two-dose (2D) vaccination schedules. The results obtained in this study were consistent with the clinical evaluation of this sMVA-based SARS-CoV-2 vaccine.

COH04S1-mediated vaccine protection in hamsters after sublethal challenge with SARS-CoV-2. a. Change in body weight. The body weight of animals vaccinated against COH04S1-IM and COH04S1-IN as well as unvaccinated control animals and sMVA-IM and sMVA-IN was measured daily for 10 days after challenge. Weight loss is reported as a mean ± SD. A two-way ANOVA followed by Tukey’s multiple comparison test was used to compare group mean values ​​at each time point. b. Maximum weight loss. The percentage of maximum weight loss is indicated in animals only of the vaccinated and control groups. Lines and bars represent median values ​​and 95% CI, respectively. The dotted line represents the maximum weight loss allowed before euthanasia. Peak weight loss in each group was compared using one-way analysis of variance followed by Tukey’s multiple comparison test. CD. Pulmonary viral loads. Copies of genomic RNA (gRNA) and subgenomic RNA (sgRNA) of SARS-CoV-2 were quantified in lung tissue of the vaccinated and control groups on day 10 post challenge by qPCR. Bars show the geometric mean of RNA copies ± geometric SD. Dashed lines represent a lower limit of detection. The Kruskal-Wallis test followed by Dunn’s multiple comparison test was used. eh. Histopathological findings. Hematoxylin / eosin stained lung sections from hamsters and control animals vaccinated with COH04S1 on day 10 post challenge were evaluated by a certified pathologist and the microscopic results were graded according to severity on a scale of. 1 to 5 (Table S2). Panel e shows the cumulative pathology score of all histopathological findings in each group. Panel F shows the ranking of the severity of bronchio-alveolar hyperplasia disease in each group. One-way ANOVA followed by the Holm-Sidak multiple comparison test was used. Panel g shows the severity of pulmonary inflammatory microscopic findings based on a scale of 1 to 5 of four types of inflammation, as shown. Bars in, for example, represent mean values ​​± SD. One-way ANOVA followed by Tukey’s multiple comparison test was used. In bf * = 0.05

h shows representative images of histopathologic findings in lung sections of animals vaccinated with COH04S1 and control animals. Black arrows indicate moderate and mild bronchio-alveolar hyperplasia in lung sections of sMVA-IM and sMVA-IN control animals as well as COH04S1-IN animals. Black arrows in lung sections of unvaccinated control animals indicate hyperplastic alveolar cells. 10x magnification.

IM and IN vaccination of Syrian hamsters with COH04S1 induced strong humoral immunity specific to the Th1 biased antigen, as well as crossed NAbs. Animals were found to be protected against reduced body weight, lower respiratory tract infections, and lung injury after the IN SARS-CoV-2 challenge.

The researchers also found that the 1D and 2D vaccines induced potent antigen-specific binding antibodies, NAbs, and Th1-biased T cells. These immune cells strongly provided protection against upper and lower respiratory tract infections.

Conclusion

The current study has developed COH04S1, which is a synthetic, multiantigen MVA-based SARS-CoV-2 vaccine that targets the S and N antigens of SARS-CoV-2. The efficacy of the newly developed vaccine was determined using animal models.

Current research has shown that the COH04S1 vaccine offers protection through different routes and dosage schedules. The results supplemented ongoing clinical trials of the SARS-CoV-2 multiantigen vaccine.

COH04S1 represents a second generation COVID-19 vaccine candidate that could be used alone or in combination with other existing vaccines to elicit protective immune responses against SARS-CoV-2. The authors of this study are optimistic that this vaccine would establish a stable, long-term immune response to prevent COVID-19.

*Important Notice

bioRxiv publishes preliminary scientific reports that are not peer reviewed and, therefore, should not be considered conclusive, guide clinical practice / health-related behavior, or treated as established information.

About Hector Hedgepeth

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