Designing Anti-Viral Vaccines that Harness Intrastructural Help from Prior BCG Vaccination

Vaccines are among the most effective tools for combatting the impact and spread of infectious diseases. However, the effectiveness of a vaccine can be diminished by vaccine inequality, particularly during severe outbreaks of infectious diseases in resource-poor areas. As seen in many developing countries that lack adequate healthcare infrastructure and economic resources, the acquisition and distribution of potentially life-saving vaccines may be limited, leading to prolonged suffering and increased deaths. To improve vaccine equity, vaccine design must take into consideration the logistics needed to implement a successful vaccination drive, particularly among the most vulnerable populations. In the manuscript titled “Exploiting Pre-Existing CD4(+) T Cell Help from Bacille Calmette-Guérin Vaccination to Improve Antiviral Antibody Responses” published in the Journal of Immunology, the authors designed a recombinant subunit vaccine against the Ebola virus (EBOV) glycoprotein that can harness the pre-existing T helper cells from prior BCG vaccination. As a recombinant subunit vaccine adjuvanted with alum, this approach has many features that make it well suited for the design of vaccines for developing nations, such as relative ease of production, scalability, and distribution. In addition, the high prevalence of BCG immunization and natural immunity to mycobacteria in many regions of the world endow such vaccines with features that should increase potency and efficacy among populations residing in such regions. As a result of using the helper activity of pre-existing BCG-specific Th cells to drive antibody responses, a lower vaccine dose is needed, which is a major advantage for vaccine manufacture. Furthermore, the BCG-specific Th cells also stimulate immunoglobulin class switching to IgG isotypes that have strong affinities for activating Fc-gamma receptors (FcγRs). Taken together, we propose that the design of subunit vaccines with intrastructural help from BCG-specific Th cells can improve protection against viral infection and represents a vaccine design that can be generally adapted to other emerging viral pathogens for the control and prevention of infection in many developing countries.