is a hundred times stronger than mRNA, can prevent all mutant strains, is extremely low cost, and can be stored at room temperature. Is the new crown vaccine coming?
Humans may be able to defeat the new crown ?
Recently, scientists from Stanford developed a new coronavirus nanoparticle vaccine based on ferritin , which can produce potent, long-lasting, broad-spectrum neutralizing antibodies in non-human primates.
Experimental results show that the new vaccine can induce an antibody response that is 100 times stronger than the existing mRNA vaccine .
and more importantly, which can cover all known variants of .
Paper address: doi.org/10.1101/2022.12.25.521784If it can be confirmed that it can also produce equally powerful antibodies in the human body, perhaps, the new coronavirus will become history in human society like smallpox.
By the way, the father of the funder behind this research is Xiao Zha.
Is the vaccine to end the new coronavirus coming?
Since the outbreak of the new coronavirus, scientists have made great progress in vaccine research.
Data shows that in the first year of the COVID-19 outbreak, mass vaccination prevented more than 14 million deaths.
However, the world still has an urgent need for vaccines. According to World Health Organization estimates, nearly 1 billion people around the world have not been vaccinated against SARS-CoV-2. In addition, the cost of vaccines is generally high, and low-temperature storage and transportation increase its cost, making it unaffordable for many people.
Moreover, the immunity provided by the vaccine through induction or infection will weaken over time; at the same time, the new coronavirus is an mRNA single-stranded virus and is very easy to mutate, thereby escaping the protective effect of the vaccine.
Therefore, there is a strong need for a vaccine that can provide longer-lasting immunity against all SARS-CoV-2 variants (VOCs) to protect the world's population, including children and infants.
Now, this beautiful wish is likely to become a reality.
Researchers from Biohub and Stanford have discovered a ferritin-based protein nanoparticle vaccine - Delta-C70-Ferritin-HexaPro (DCFHP).
They found that when formulated with aluminum hydroxide as the only adjuvant (DCFHP-alum), the new vaccine can elicit neutralizing antibodies against known variants (including Omicron BA.4/5, BQ.1, etc.) as well as SARS-CoV-1 in nonhuman primates (NHPs), and the effect is long-lasting.
In the enhanced immunity one year after the initial immunity , DCFHP-alum can also cause a strong antigen response.
In addition, compared with many new crown vaccines, the storage conditions of this vaccine are not harsh. Test results show that the effectiveness of DCFHP-alum can be maintained at temperatures exceeding standard room temperature for at least 14 days.
Researchers believe that DCFHP-alum can not only be used as a once-a-year booster shot later, but is also very safe for children (including infants).
Why is it a protein nanoparticle vaccine?
Compared with subunit vaccines, protein nanoparticle vaccines are more easily absorbed by dendritic cells presented with antigen , and the nanoparticles promote multivalent presentation of the antigen, promote the aggregation of receptor and subsequent B cell activation.
Currently, this ferritin-based nanoparticle vaccine has shown a strong humoral immune response to SARS-CoV-2 and other viral glycoproteins, and also has a high safety profile in clinical trials.
Previously, this group of researchers had tried a nanoparticle vaccine based on the protein -SΔC-Fer.
SΔC-Fer contains a mutated furin cleavage site and a prefusion stable replacement for 2-proline (2P) (also found in the FDA-approved SARS-CoV-2 mRNA vaccine).
What is particularly important is that SΔC-Fer also deletes 70 amino acid residues at the C terminus of the spike protein extracellular domain (spike ectodomain).
spike (S) is a structural glycoprotein expressed on the surface of SARS-CoV-2 and is a key determinant of the host and tissue tropism of the virus. SARS-CoV-2 S mediates virus entry into target cells after binding to the ACE2 receptor, and is therefore a potential therapeutic drug target. The residues deleted by contain immunodominant, linear (non-conformational) epitopes. In convalescent COVID-19 plasma, these epitopes are often targeted by antibodies.
Compared with other vaccines, if these immunodominant linear epitopes are removed from the ferritin nanoparticles and the multivalent presentation of the modified spike protein is performed, the neutralizing efficacy of induced antibodies in mice will be greatly improved.
Upgrade SΔC-Fer to DCFHP
In this experiment, the researchers used an upgraded version of SΔC-Fer, Delta-C70-Ferritin-HexaPro, or DCFHP.
They supplemented the 2P stabilizing substitute with the four proline substitutes mentioned above to create a six proline substitute (HexaPro) version.
DCFHP schematic, including modifications to convert SΔC-Fer to DCFHPThe above work shows that the HexaPro SARS-CoV-2 spike protein has higher stability and better expression relative to the 2P version.
In addition, DCFHP is also more stable than SΔC-FER under temperature changes.
Experimental results showed that DCFHP-alum induced a strong and long-lasting immune response against SARS-CoV-2 variants in mice.
In addition, through the immunization of mice, the researchers found that DCFHP-alum can maintain stability for at least 14 days in the temperature range of 4°C to 37°C.
Therefore, it can be speculated that the DCFHP-alum vaccine does not require refrigeration. Three-dimensional reconstructed cryo-electron microscopy density map of
DCFHP Subsequently, the researchers conducted experiments in rhesus monkey .
produced durable, powerful neutralizing antibodies, including Omicron BA.4/5 37 and BQ.1, after two doses of intramuscular immunization of rhesus monkeys with DCFHP-alum, as well as a balanced Th1 and Th2 immune response.
What is most surprising is that these non-human primate (NHP) antibodies also showed strong and long-lasting neutralizing activity against different SARS-CoV-1 pseudovirus variants.
About a year later, the researchers boosted the rhesus monkeys with a third dose of DCFHP-alum, which also produced a strong, broad-spectrum neutralizing antibody response in their bodies.
In other words, DCFHP-alum can not only act on various variants of the new coronavirus, but also promote the vaccination of the new coronavirus around the world.
This solution is very cost-effective and only requires a booster shot every year.
Experimental results are surprising
To study the stability of the DCFHP-alum vaccine, the researchers stored samples at 4˚C, 27˚C, or 37˚C for different times and evaluated the immunogenicity of these stored samples in a single-dose mouse immunity study.
Notably, in pseudovirus neutralization trials, the DCFHP-alum vaccine maintained similar immunogenicity at all temperatures and storage periods.
Therefore, the researchers concluded that DCFHP-alum is still stable after two weeks of storage at 37˚C.
The researchers selected 10 male rhesus monkeys aged between 3 and 9 years old and divided them into two groups (A, B).
First, two groups of rhesus monkeys were initially immunized on day 0, and then booster shots were given on day 21 (group A) or day 92 (group B) (Figure 3A).
Rhesus monkeys that received the booster shot later could produce better neutralizing antibodies (Figure 3C and D) based on the evaluation 14 days after the booster immunization (Figure 3C and D); on average, the neutralizing response of group B to different variants increased approximately 4-fold relative to group A.
In further studies, it was found that all nonhuman primates had neutralizing antibody responses to the original strain that lasted for at least 250 days (Figure 4A and C).
Similarly, most animals in group B maintained detectable neutralizing potency against BA.4/5 and sequence-distinct SARS-CoV-1 for approximately one year (Figure 4D), and their titers were generally higher than those in group A (Figure 4B).
To determine whether DCFHP-alum could be used as an annual vaccine, the researchers gave all rhesus monkeys another booster shot on day 381.
The results showed that both group A and group B rhesus monkeys showed strong immune responses. The average NT50 values for the original strain, BA.4/5, SARS-CoV-1, and BQ.1 were approximately 10^4, 10^3.5, 10^3, and 10^3, respectively (Figure 5A-H).
To summarize
researchers said that although the DCFHP-alum vaccine is based on the earliest The original strain sequence, but can trigger a strong and broad-spectrum neutralizing antibody response to SARS-CoV-2 variants and SARS-CoV-1 (including against BA.4/5, BQ.1 and SARS-CoV-1) in non-human primates, and can last for more than 250 days.
Since DCFHP-alum provides primary immunity to non-human primates and can provide very broad protection against new coronavirus variants, DCFHP-alum can be used as an important primary prevention vaccine for unvaccinated or uninfected people.
At the same time, the excellent safety profile of aluminum salt adjuvants has been demonstrated over the past decades as part of routine childhood immunization programs, and they are also commonly used ingredients in infant vaccines. Therefore, DCFHP-alum may also be an ideal way to help establish an immune signature against SARS-CoV-2 in infants.
In addition, CHO-based cell lines enable low-cost, large-scale production of new vaccines and are also stable for more than two weeks at temperatures above standard room temperature.
In summary, the researchers believe that DCFHP-alum is an excellent candidate for the development of a new vaccine for .
Source of this article: Xinzhiyuan et al.
