The first study reports results with a modified version of the Ankara vector vaccinia and was published in Immunity on February 3. The second is a candidate of DNA-based, self-replicating vaccine, published in Scientific Reports on 4 February.
Although significant progress has been made in the development of vaccines in the wake of COVID-19 pandemic disease, many challenges remain associated with the development of new vaccines. These include:
- Lack of long-term safety and immunogenicity data in humans
- Poor entry of CD8 + T-cell response
- Lack of reactive immunity against other human coronaviruses
- Failure to provide protection against SARS-CoV-2 reproduction in the nasopharynx
- Cold storage required
“Although several vaccines against COVID-19 have been approved for emergency use, there are still concerns about the stability of immune responses after vaccination,” said Inga Szurgot, PhD, author of the Scientific Reports article and professor in the department of microbiology, tumors, and cell biology at the Karolinska Institut, in a statement. “In addition, the mRNA molecule-based vaccines must be stored and transported at ultralow temperatures. Maintaining such a condition can cause supply problems and may not be possible even in many areas. of the world where vaccines are desperately needed. “
MVA / S COVID-19 vaccine
Researchers at Emer University’s Yerkes National Priority Research Center have developed a vaccine that is safe and effective in mice and monkeys. The vaccine uses Ancinara-enhanced bacteria (MVA) vaccinia that express stable spike proteins (MVA / S) anchored by organs.
MVA is very resistant to the vaccinia virus. They recover well, usually stimulate strong, stable antibody and T-cell responses, and can be delivered through multiple pathways. In addition, they can contain large genetic substances that allow the expression of several antigens and can make high titer vaccines for easy cultivation.
In the study, the Emory vector-based vaccine at MVA was shown to stimulate both neutral antibodies and CD8 + T cells in the blood and lungs. Vaccination induces strong anti-neutral antibody responses against SARS-CoV-2 in mice. And in macaques, vaccination with the MVA / S stimulated two-dose strong neutral antibodies and CD8 + T-cell responses. The MVA / S vaccine also protected against SARS-CoV-2 infection and viral reproduction in the lung as early as two days after intranasal or intratracheal challenge.
“Comparing the virus in vaccine and placebo groups gave clear results that the MVA / S vaccine is safe and effective against SARS-CoV-2,” said Rama Amara, PhD, researcher in the department of microbiology and immunology of Yerkes and the Emory Vaccine Center. “These results are even more promising because the MVA / S vaccinated animals showed no signs of inflammation in the lungs like what medical professionals see in people with COVID-19.”
Single-cell RNA sequence analysis of lung cells at day four after infection showed that MVA / S vaccine also protected macaques from inflammation that caused infection and reduced B-cell dysfunction and reduced induction of interferon-stimulated genes.
The group will continue its work on developing the MVA vaccine, with a focus on single-dose production. They are also working on inserting several genes of the coronavirus into the vaccine to increase its ability to secrete T-cell responses.
DREP-S COVID-19 vaccine
In a separate report, scientists at the Karolinska Institute in Sweden describe the effectiveness of a prototype vaccine against SARS-CoV-2 using a cheap, stable, easy-to-administer DNA vaccination platform. result, and which reflects a good safety image.
The vaccine is based on DNA – launched self – expanding RNA vector (DREP) vaccine, which encodes the SARS – CoV – 2 glycoprotein spike vaccine (DREP – S). The platform uses the alphavirus genome derived from the Semliki Forest virus (SFV) and encodes the genes for viral RNA replication but does not encode the genes for the structural proteins of the virus.
When delivered, DNA-activated RNA molecules reproduce in the same way as they would at the time of alphavirus infection, with the important difference that new viral fragments are not formed. The self-expanding replica vectors have sexually transmitted traits and promote apoptosis of transfusion cells.
DREPs are well-suited for rapid vaccine development because they can accept any interesting antigen encoding and require lower doses compared to traditional DNA vaccines. Importantly, an applicant does not need the cold chain vaccine during transport and storage. The platform is managed as naked DNA and is suitable for rapid modification so that new viruses or potential threats in an emerging revolution can be quickly targeted.
In the study, the DREP-S vaccine stimulated both binding and neutral antibodies as well as T-cell responses. DREP-S-elicited antibodies were able to effectively neutralize the pseudotyped SARS-CoV-2 virus in four out of five mice. These high titers of SARS-CoV-2 specific immunoglobulin G (IgG) antibodies were able to effectively neutralize pseudotyped virus after a single vaccination. The researcher found that main-dose responses were induced by administration of a heterologous spike protein vaccine.
The authors noted that DREP-based vaccines mainly drive T-helper type 1 (Th1) cellular responses, which have favorable antiviral properties. In addition, DREP vaccine candidates already stimulated a strong cellular response against S1 domain of the spike protein after a single vaccination.
“Different vaccine treatments and platforms have the distinct advantages and may work homogeneously in governments where a patient receives the first vaccine with one type of vaccine and the second with a different type, “lead author Peter Liljestrom, PhD, professor of microbiology, tumor, and cell biology department at the Karolinska Institute, said:” This approach often provides a better and more responsive response.
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