Kim expects this vaccine to work just as well as the first version that infants receive. The immune response can become more protective, Kim said.
This vaccine provided immunity in rhesus monkeys against SARS-CoV-1, a distant relative of the SARS-CoV-2 lineage. Unlike Pfizer/Biontech and Moderna’s bivalent mRNA vaccines, which include the original Wuhan strain and the latest variants, DCFHP Alum was developed using only the first strain of the spike protein.
Such an approach avoids “variant chase,” where researchers keep changing booster recipes as the virus mutates.
“What’s interesting is that people are tired of being vaccinated every three to four months, so if these results apply to humans, they could boost herd immunity,” Kim said. says.
In developing the DCFHP-alum vaccine, scientists made several modifications to the spikes found on the surface of the coronavirus.
They stabilized Spike first. In hijacking cells to create new viral particles, coronaviruses use surface spikes to grab proteins in cells. When proteins attach to the spike, the spike turns inside out and fuses with the cell. By modifying the spikes to make them stiffer and prevent them from turning inside out, vaccines can prevent this tampering.
The second modification was to fuse ferritin, a nanoparticle that presents antigens to the immune system, to the spike. Using nanoparticles in addition to stabilizing the spike protein is a better stimulator of the immune system, Kim said, because the nanoparticles are captured by dendritic cells. These cells capture foreign antigens and transport them to lymph nodes where they encounter her B and T cells, which are essential components of the immune response.
A third change is that the researchers removed the last 70 amino acids (the building blocks of the protein) of the spike closest to the viral membrane. Kim described the area as “a distraction for the immune system.” People have a strong antibody response to this area, but the antibodies produced do not neutralize the virus. By removing that portion of the protein, the scientists’ hypothesis was that the vaccine would stimulate the immune system to make more antibodies that neutralize the virus.
Once the vaccine was developed, the team immunized 10 male rhesus monkeys and divided them into two groups. Animals were then tested for antibodies that confer immunity to the virus. Both showed resistance after vaccination, which lasted for at least 250 days. Boosters administered after 92 days elicited stronger immune responses than those administered after 21 days.
The researchers gave the monkeys a second booster on day 381. This largely eliminated the differences in immune responses seen between the two groups. Both showed significant immune responses after the second booster, indicating immune system memory.
Kim hopes people will see equally promising results.
“If we pass clinical trials with this promising vaccine, we will be able to target a large portion of the world’s unvaccinated population, or those in need of a booster,” Kim said.
Researchers from the University of Kansas, the California Department of Public Health, the New Iberia Research Center, the International AIDS Vaccine Initiative, the University of Louisiana at Lafayette, and the Chan Zuckerberg Biohub contributed to this work.
This study was funded by the Frank Quattrone & Denise Foderaro Family Research Fund, Chan Zuckerberg Biohub, Stanford Innovative Medicines Accelerator, Virginia & DK Ludwig Fund for Cancer Research, and the National Institutes of Health Director’s Pioneer Award (DP1AI158125).
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