aniel Norero reports for the Genetic Literacy Project that the first work to develop an algae-based vaccine comes from Italy, one of the countries hardest hit by the COVID-19 pandemic. The research is being carried out by the Laboratory of Photosynthesis and Bioenergy of the Department of Biotechnology at the University of Verona, directed by professors Roberto Bassi and Luca Dall’Osto.
This laboratory works with a wide range of phototrophic organisms, including unicellular algae, mosses and higher plants, and also has a strong line of genetic engineering in model plants and unicellular algae to express recombinant products and enzymes with industrial and renewable energy applications.
“The ability to perform genetic engineering, especially on the single-celled alga of the model organism Chlamydomonas reinhardtii, has provided the basis for contributing to the development of an oral vaccine against the recently emerged SARS-VOC-2 viral strain responsible for the current pandemic threatening the global health,” said Dr. Edoardo Cutolo in a detailed interview with the Alliance for Science. This pioneering project involves Dr. Cutolo’s colleague, Dr. Max Angstenberger, in addition to the support of Dr. Simone Barera.
The scientific team applied two different approaches to introduce a DNA sequence that encodes an antigen derived from SARS-COV-2 into the microalgae genome. The antigen, in this case, is a protein or a protein portion that produces a response immune in our body, finally generating antibodies against the virus. The inserted DNA sequence corresponds to a portion of the Receptor Binding Domain (RBD) of the viral spike protein from the famous virus, required to bind to the ACE2 receptor and thus enter and infect host cells.
“We use both conventional nuclear transgenesis and chloroplast transformation. In the second case, we aim at integrating the transgene inside the semi-autonomous polyploid genome of the photosynthetic organelle,” Dr. Cutolo said. “In the case of Chlamydomonas reinhardtii, the chloroplast represents the largest cell compartment, and since it is made of multiple copies of a circular chromosome, it leads to the accumulation of higher levels of recombinant proteins compared to transgenesis in the nucleus.”
Both methods have advantages and disadvantages. On the one hand, the chloroplast not only allows greater accumulation of the antigen necessary for a vaccine due to its large size in the microalgae, but also facilitates a more stable integration of the transgene, avoiding the random integration problems most common when the nucleus is genetically modified. But on the other hand, the cell nucleus has a machinery that allows subsequent modifications, such as glycosylation, of the new protein (or antigen), giving it functionality to generate adequate immunization.
“Of note, in this project we employ selection methods that don’t rely on antibiotic resistance genes,” Dr. Cutolo said in reference to a supposed risk widely cited by critics of this technology. “But we exploit the metabolic flexibility of this organism and a novel selectable marker strategy based on the selective metabolism of an essential nutrient to produce algae that comply with both health and environmental related concerns.”
According to Dr. Cutolo, if contamination is prevented, it is possible to accumulate up to 1 mg of the recombinant antigen for each gram of biomass of dried algae. Subsequently, the dehydrated/lyophilized algae can be encapsulated to generate an “oral vaccine.”
“The cell wall from the dry algae protects the antigens from the harsh acidic and protease-rich gastric environment, enabling the bioactive molecule to reach the intestinal immune system where it can stimulate cellular and humoral responses, hopefully, leading to effective immunization,” Dr. Cutolo explained.
When could they have an oral vaccine ready to test on animals? “Very soon,” he says. “Six weeks is a probable date.”