Conducted in partnership with the Institute Pasteur of São Paulo, the study uses an experimental model to demonstrate that inducing T cell response is possible and could help develop more universal vaccines.
An article published in the scientific journal Viruses presents an unprecedented DNA vaccine against Covid-19, specifically developed to induce T cell response– crucial components of the immune system responsible for identifying and eliminating infected cells. The study was conducted in partnership between the Institut Pasteur de São Paulo (IPSP), the Institute of Biomedical Sciences of the University of São Paulo (ICB-USP), and the biotechnology company ImunoTera. At IPSP, the research was led by Rúbens Alves, an immunologist and virologist who coordinates the Genomic Surveillance and Vaccine Innovation group.
According to Alves, the work provides a unique proof of concept for a vaccine capable of generating T cell responses. “During the pandemic, Covid-19 vaccines induced antibodies and, as a secondary effect, T cell response. We’ve shown that it’s possible to design a vaccine that targets this specific response, which opens up new opportunities to combat viruses and even virus-induced cancers in a more comprehensive way,” he explains.
The idea emerged shortly after the first sequence of SARS-CoV-2 was released. Inspired by the experience gained during his internship at the La Jolla Institute for Immunology, Alves and his colleagues proposed that, instead of solely targeting the virus’ “shell” (including the Spike protein), it was also crucial to target its “engine”: the more conserved internal regions, which tend to change less over time. These regions were selected based on the most common HLA molecules in the Brazilian population, enhancing the vaccine’s effect in the immune system of the local inhabitants.
In the experiments, the researchers developed a DNA vaccine that combined these conserved internal regions of SARS-CoV-2 and genetically fused them to the herpes simplex virus (HSV-1) glycoprotein D, used as an adjuvant to enhance immune activation. Applied to mice via electroporation, the vaccine induced highly functional T cells capable of producing interferon-gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α).
When challenged with the virus, the vaccinated animals showed less weight loss, better clinical scores, and reduced viral load in the lungs and brain compared to controls, guaranteeing partial short-term protection, with 60% survival in a late challenge (5 weeks after immunization). In additional tests, experimental removal of T cells led to the loss of this effect, confirming that this arm of the immune response was primarily responsible for the protection.
Impact for future vaccines – The findings reinforce the importance of considering cellular immunity in the development of next-generation vaccines. While antibodies act as “guards” that prevent viruses from entering cells, T cells function as a “surveillance body,” eliminating infected cells. This strategy of targeting T cells could have an impact in a variety of scenarios beyond COVID-19.
In intracellular pathogens, such as certain viruses and bacteria that replicate inside cells, external antibodies cannot act effectively—and this is precisely where T cells are crucial. In the case of cancers associated with viruses, such as HPV, it is even more important: since these viruses remain inside cells, it is T cells’ role to recognize and eliminate infected or transformed cells. In diseases like dengue, if antibodies are not specific enough, they end up facilitating viral replication rather than neutralizing it. In these cases, the induction of CD8 T cells becomes crucial to prevent immune imbalances and offer protection against different serotypes.
Scientific collaboration – The project began in 2020 at the Vaccine Development Laboratory (LDV) of ICB-USP, under the coordination of Professor Luís Carlos Ferreira. Rúbens Alves, who had the original idea, conducted the first proof-of-concept experiments. Subsequently, Luana Raposo de Melo Moraes Aps, the CEO of ImunoTera, a spin-off incubated at LDV and the paper’s first author, joined as a strategic partner: in addition to her experience studying the gD adjuvant in cancer vaccines, she took responsibility for part of the animal experiments and shared with Alves the filing of the patent application protecting the formulation.
Later, at the Institut Pasteur de São Paulo, Alves was able to rely on the high-containment (NB3) infrastructure, essential for SARS-CoV-2 challenge tests. This trajectory reinforces how collaboration between different institutions has been decisive for consolidating the results and paving the way for the development of more universal, durable vaccines targeted at specific populations – an increasingly urgent concern, given the threat of new epidemics and pandemics.
“We were able to show that a vaccine designed to activate T cells and target parts of the virus that don’t change much can reduce diseases in animal models, which adds to the tradition approach for vaccine development and aligns with the genetic reality of the Brazilian population,” summarizes Alves.