Vaccination is undoubtedly the most effective approach for dealing with infectious diseases. However, more than two centuries after the introduction of the first vaccine (the smallpox vaccine of Edward Jenner), there remain many important infections for which there are no adequate vaccines or no vaccines at all. They include rapidly evolving pathogens such as influenza viruses (flu), coronaviruses (COVID and common cold), RSV (inflammation of airways and pneumonia), and HIV-1 (AIDS).
We have proposed a novel paradigm of vaccination that involves the deployment of regulated microbes (1). Traditional vaccines employ attenuated microbes, inactivated microbes, or parts thereof. To some extent, such vaccines trade efficacy for safety. They largely protect against the variant of the pathogenic microbe for which they were designed. Messenger RNA vaccines are different but the breath of protection is comparable to that of traditional vaccines. A regulated microbe vaccine is not attenuated and is, therefore, capable of inducing a strong and balanced immune response (in the absence of an adjuvant). Safety is provided by a two-pronged mechanism that can be deliberately actuated and that restricts the replication of the microbe both spatially and temporally (2). We explored heat-activated or co-activated microbe vaccines that were based on a virulent herpes simplex virus type 1 strain/. In animal studies, the vaccines had potent ant-herpetic efficacy (3), and when expressing a full-length influenza A virus hemagglutinin protected across influenza A virus groups. Protection even extended to influenza B. The vaccine effects were largely antibody-mediated and elevated titers of broadly neutralizing antibodies were induced by the vaccines. It is noted that the vaccines were administered epidermally and may, therefore, be applied in a needle-free fashion, e.g., by means of a microneedle patch. Results obtained suggest that the novel vaccine technology may support the development of universal flu vaccines that may also double as anti-herpetic vaccines. The vaccines may also serve as pandemic vaccines. The technology may potentially be employed to prepare effective vaccines against other rapidly evolving viral pathogens, including coronaviruses (SARS-CoV-2), RSV, HIV-1, and others.
Hypothesis and work already published:
1. Voellmy R, Bloom DC. Vilaboa N. (2015) Expert Rev. Vaccines. 14: 637-51
2. Bloom DC, Feller, J, McAnany P, Vilaboa N, Voellmy R. (2015) J Virol. 89: 10668-79
3. Bloom DC, Tran RK, Feller J, Voellmy, R. (2018) J Virol. 9(16): e00616-18