COVID-19 vaccine developed at University of São Paulo presents promising results in animal trials
The vaccine formulation has proved to be highly protective, safe and versatile. Moreover, it can serve as a basis for the development of zika and dengue vaccines, for example
Studies conducted in mice have shown that the COVID-19 vaccine being developed by researchers at the University of São Paulo’s Medical School (FM-USP) in Brazil is safe and efficacious. The vaccine triggered a satisfactory immune response against the pathogen in the mice and protected them from infection. An article describing the results is published in the journal Scientific Reports.
“Most vaccines are based on attenuated or inactivated viruses, but our next-generation strategy enables us to prioritize not just safety and efficacy but also plasticity in the formulation so that the vaccine can easily be updated to combat variants of concern,” said Gustavo Cabral de Miranda, principal investigator for the project, which is supported by FAPESP and hosted by the Immunology Laboratory in the Institute of Tropical Medicine (IMT-FM-USP).
The strategy used by the researchers at FM-USP to develop the vaccine deploys virus-like particles (VLPs). “VLPs have similar characteristics to viruses but without viral genetic material, so although they’re recognized by the immune system, they cannot replicate or cause disease,” Cabral said.
VLPs can serve as vaccines on their own, or they can be conjugated with an antigen (a protein that stimulates the immune system to produce antibodies), as in this specific case. “Under certain conditions in the lab, structural surface proteins are capable of converting themselves into VLPs. They can be produced in the lab using bacteria that act as miniature factories to stimulate this transformation. A second step entails inoculation of the antigen, which is the spike protein in the case of COVID-19. This facilitates the entire process, makes it flexible, and lowers the cost of developing the vaccine,” he said.
Another advantage of the COVID-19 vaccine, according to Cabral, is that it does not require an adjuvant to enhance the body’s immune response to the antigen. “In both the in vitro and in vivo tests, we designed strategies to keep the cost of formulation low and use the smallest possible amount of inputs not developed in our own lab. The vaccine doesn’t require an adjuvant, for example,” he said.
Besides part of the virus they are designed to combat, or molecules that mimic the virus such as VLPs, vaccines contain various other compounds that stimulate the immune response, especially adjuvants. The most common adjuvant is aluminum hydroxide, which has been used in vaccines worldwide for more than 100 years. “Opting for the development of a self-adjuvanted vaccine enables us to avoid dependency on the companies that produce adjuvants and lowers the cost of the formulation,” he said.
The group of researchers at FM-USP aims to produce knowledge for use by a platform that can develop several other vaccines. “VLPs constitute a highly flexible technology. In this case, for example, we can simply remove the antigen [a piece of the SARS-CoV-2 spike protein] and replace it with a protein from zika virus,” Cabral explained. “There’s nothing hypothetical about this example. We’re developing such a vaccine at our lab. It’s no simple task, of course, but a platform for the development of several vaccines can be based on this technology.”
About FAPESP
The São Paulo Research Foundation (FAPESP) is a public institution with the mission of supporting scientific research in all fields of knowledge by awarding scholarships, fellowships and grants to investigators linked with higher education and research institutions in the state of São Paulo, Brazil. FAPESP is aware that the very best research can only be done by working with the best researchers internationally. Therefore, it has established partnerships with funding agencies, higher education, private companies, and research organizations in other countries known for the quality of their research and has been encouraging scientists funded by its grants to further develop their international collaboration.
Journal
Scientific Reports
Article Title
A self-adjuvanted VLPs-based Covid-19 vaccine proven versatile, safe, and highly protective
Wrong place, wrong time: Why Zika virus hijacks a protein needed for brain growth
University of California - Davis
The mosquito-borne Zika virus is known for causing microcephaly, a birth defect in which abnormal brain development results in a smaller-than-expected head. A new study published Jan. 13 in mBio shows that the Zika virus hijacks a host protein called ANKLE2, which happens to be important for brain development, to assist its own reproduction. Because Zika, unlike most related viruses, can cross the placenta, this can have disastrous consequences in pregnancy.
“It’s a case of Zika being in the wrong place at the wrong time,” said Priya Shah, associate professor in the departments of Microbiology and Molecular Genetics and of Chemical Engineering at the University of California, Davis and senior author on the paper.
The new work shows that related viruses, including dengue virus and yellow fever virus, also use ANKLE2 for the same purpose. The discovery could open the way to new strategies to develop vaccines or therapeutics against these viruses.
Viruses carry only a limited set of instructions in their own genetic material, so to reproduce they rely on taking over host cell proteins and functions. Shah’s laboratory studies these interactions between virus and host.
Shah and her research team previously found that a Zika virus protein called NS4A interacts with ANKLE2 in host cells. Working in Drosophila fruit flies, they showed that this could lead to microcephaly.
ANKLE2 is known to be involved in brain development in the fetus, but is found in cells throughout the body.
Forming virus factories
In the new study, led by recent Ph.D. graduate Adam Fishburn, Shah’s team grew Zika virus in human cells. Knocking out the ANKLE2 gene in these cells reduced the ability of Zika virus to grow.
In Zika-infected cells, ANKLE2 clusters in pockets around the endoplasmic reticulum, a network used for protein production within the cell.
Viral NS4A interacts with ANKLE2 to form pockets off the endoplasmic reticulum that act as virus factories, Shah said. Bringing all the components to make viruses in one place makes replication more efficient and also helps hide the virus from the immune system.
“Our current model is that ANKLE2 is really important, but not essential, for forming these replication pockets,” Shah said.
Our cells are well equipped to fight off these viruses, but only if they can find them, Fishburn said.
“Zika and related viruses have evolved strategies to hide themselves in these replication pockets to avoid detection. We believe that ANKLE2 is hijacked to help facilitate this process, and without it the pockets don’t form as well and the immune system can keep virus replication in check,” Fishburn said.
Working with Claudia Rückert at the University of Nevada, Reno, they found that Zika virus also uses ANKLE2 when it infects mosquito cells, meaning that this interaction is important in both human and insect hosts. Finally, they showed that NS4A from other, related mosquito-borne viruses, including dengue virus and yellow fever virus, interacts with ANKLE2 in the same way. This all suggests that NS4A/ANKLE2 interaction is important for replication across a broad group of mosquito-borne viruses, opening possible routes to new drugs and vaccines for these diseases.
If much more common viruses like dengue virus also target ANKLE2, why don’t they also cause the microcephaly seen in Zika virus infection? It’s probably all down to location. Zika virus is unusual in that it can cross the placenta and enter the fetus, where ANKLE2 is known to play a big role in brain development. Most other viruses are kept out of the fetus by the placental barrier.
The work was supported by grants from the National Institutes of Health and the W. M. Keck Foundation. Additional authors on the paper are: Cole Florio, Thomas Klaessens, Neil Alvin Adia, Nicholas Lopez, Nitin Sai Beesabathuni, Sydney Becker, Liubov Cherkaschenko, Sophia Haggard Arcé, Vivian Hoang and Traci Shiu at UC Davis; Brian Prince, University of Nevada, Reno; and Blake Richardson and Matthew Evans at Icahn School of Medicine at Mount Sinai, New York.
Journal
mBio
Method of Research
Experimental study
Subject of Research
Cells
Article Title
Microcephaly protein ANKLE2 promotes Zika virus replication
Article Publication Date
13-Jan-2025
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