In the case of COVID-19, caused by the virus SARS-CoV-2, researchers at Baylor College of Medicine and Texas Children's Hospital have found that vaccine design can face specific challenges and that vaccine development approaches require an understanding of how the immune system naturally responds to a specific infection as well as how vaccines might trigger specific protective responses.
..Preclinical testing of some experimental vaccines followed by viral infection in animal models showed tissue damage caused by cellular infiltrates after the induction of an immune response...
"Some experimental animals developed an inflammatory response in the lung or liver characterized by significant infiltration of immune cells -- lymphocytes, monocytes and eosinophils," Corry said. "Our literature search suggests that this cellular infiltration can be associated with IL-6, a cytokine or immune protein that is strongly increased in patients with COVID-19 who experience a cytokine storm, an excessive production of cytokines that can be life-threatening
"We also found studies that show that type Th17 immune responses likely could account for the cellular infiltrates, including eosinophils, observed in animal models," said Hotez.
This immune infiltration was observed with experimental viral-vectored vaccines. Viral-vectored vaccines use a chemically weakened and different virus to transport components or antigens of the COVID-19 virus into the body to stimulate an immune response.
Although more research is needed to understand the mechanisms of cell-mediated responses and their relevance to clinical outcomes, the potential of significant immune cell infiltration has important implications for COVID-19 vaccine development.
...Called antibody-dependent enhancement, this response has been previously observed in dengue and other viral infections..
Whether this phenomenon is relevant to human coronavirus infection is unclear. In laboratory experiments, antibody-dependent enhancement seems to occur with both non-neutralizing and neutralizing antibodies.
"For this reason, we selected the receptor binding domain of the virus. It excludes the epitopes or sections of viral proteins that might potentially induce antibody-dependent enhancement," Hotez said."
Сами исследователи выбрали мишенью антигены, которые не вызывают АЗУ, вызывают достаточную выработку антител, и думают использовать адьювант, угнетающий активацию клеточного иммунитета. Пока, на животных, вроде бы все выглядит обещающе:
...We have not found any evidence that our vaccine triggers antibody-dependent enhancement in laboratory pre-clinical experiments. Experimental evidence suggests that our vaccine against the receptor binding domain leads to the neutralization of the virus..It can trigger an immune response that is protective and does not induce undesirable cellular immune responses. We are working to advance this approach into the clinic for phase 1 studies."