Bacteriophages and phage-like particles are the basis of various diagnostic and therapeutic systems. For example, phage-like particles were used to create a plague vaccine—they carried antigens of the disease-causing bacterium Yersinia pestis on their surface.

Scientists from the University of Colorado and the University of Maryland announced* the development of a monovalent vaccine based on phage-like particles carrying surface antigens from the receptor-binding domain of the SARS-CoV-2 virus (RBD SARS PLP) or another coronavirus, MERS-CoV (RBD PLP). The authors also constructed a bivalent phage-like particle containing both antigens.

To evaluate the immunogenicity of the RBD SARS PLP vaccine, scientists immunized 6-week-old BALB/c mice with it and a control vaccine containing unmodified phage-like particles. Three weeks later, the mice received a second dose.

After the first dose of RBD SARS PLP, the titer of specific antibodies (IgG) against the receptor-binding domain of the SARS-CoV-2 virus was close to that in patients who recovered from COVID-19.

In a special test, the authors tested the neutralization potential of serum from mice in the control and experimental groups. Serum from animals receiving unmodified phage-like particles (lacking the SARS-CoV-2 coronavirus antigen on their surface) showed no neutralizing activity against SARS-CoV-2. Serum from mice vaccinated with RBD SARS PLP neutralized SARS-CoV-2 with an efficacy similar to that seen in patients who had recovered from COVID-19. After receiving a second (booster) dose of the vaccine, the neutralizing activity of their serum increased by 4.7 times. High antibody titers against SARS-CoV-2 persisted in the animals for at least 174 days after vaccination. This confirmed that RBD SARS PLP provides long-lasting humoral immunity.

On day 184 post-vaccination, the mice were infected with an adapted SARS-CoV-2 strain, which causes severe COVID-19. While the control group animals began to rapidly lose weight, this was not observed in the experimental group.

On day 4 post-infection, the mice were euthanized for pathological examination and viral load analysis. The lungs of control animals, in contrast to those vaccinated with RBD SARS PLP, contained a large number of viral particles, as well as significantly higher levels of genomic and subgenomic RNA. Pathological changes were also observed: the lungs of control animals showed an accumulation of immune cells around blood vessels and in the alveoli, pulmonary vascular congestion, and interstitial edema. In animals vaccinated with RBD SARS PLP, the pathological changes were significantly less pronounced, indicating that the drug protects the lungs from damage and inflammation.

The authors believe that using phage-like particles to create vaccines holds promise: such vaccines induce the synthesis of neutralizing antibodies and provide long-lasting and effective protection against virulent viruses. Such systems require further optimization and could help prevent the spread of infectious diseases.

* Davenport BJ, Catala A, Weston SM, Johnson RM et al. Phage-like particle vaccines are highly immunogenic and protect against pathogenic coronavirus infection and disease. Preprint from bioRxiv, 2021. https://doi.org/10.1101/2021.11.08.467648