Utilization of Similar Epitopes to Develop Viral Vaccines that Produce Lifelong Immunity

The half-life (HL) of specific antibodies produced by the human body against various viruses varies from about 4 months to 11,000 years. Due to their short half-lives, multiple-dose vaccinations and annual revaccination are usually required for most viruses, which cause a large economic burden, especially in developing countries with limited storage of vaccines. Protein assemblies with a high degree of repetitiveness and organization are known to induce strong and long-lasting immune responses. However, the detailed quantitative law is still unknown. Through epitope analysis of representative viruses, we found that the longevity of immunological memory may be correlated with the number of epitopes with similar sequences (EWSS). Accordingly, a vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with 4.5-times higher antibody titers and over 100 months of HL was developed in a rabbit model. The decay pattern of antibodies against each epitope or the entire SARS-CoV-2 spike protein was roughly correlated with the number of EWSS in immunization treatments, that is, for every additional EWSS, the HL of the antibody would be doubled. This study also discusses improvement measures for vaccines against other viruses.