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Regulated microbe vaccines: from concept to (pre-clinical) reduction to practice
Richard Voellmy1, David C Bloom2, Nuria Vilaboa3,4
1HSF Pharmaceuticals SA, La Tour-de-Peilz, Switzerland.
Introduction:
Vaccines to prevent important infections involving, e.g. influenza viruses, severe acute respiratory syndrome-causing coronaviruses (e.g. SARS-CoV-2), respiratory syncytial viruses (RSV), and human immunodeficiency viruses (HIV) have remained insufficiently effective or are not available at all. Regulated microbes constitute novel vaccine platforms that may be employed for the development of more potent and/or more broadly effective vaccines.
Areas Covered:
We review the development and characterization of the vaccine potential of replication-competent controlled herpesviruses (RCCVs) which represent the first examples of regulated microbes used as vaccines.
Expert Opinion:
The RCCVs developed to date are suitable for application to the skin and can be activated deliberately to replicate efficiently, but only transiently, in the administration site. Without activation, the RCCVs are incapable of replicating in the nervous system and elsewhere. The RCCVs were found to induce potent anti-herpetic immune responses in mice. Vaccination with RCCVs expressing an influenza virus hemagglutinin broadly protected animals against lethal influenza virus challenges. This protection appeared to be at least in part antibody-mediated. These findings support a rational expectation that RCCVs may be developed into universal, non-seasonal vaccines against influenza and, possibly, against other rapidly evolving pathogens.
Insights
Replication-competent controlled herpesviruses (RCCVs) show promise as novel vaccine platforms. RCCVs expressing influenza antigens protected mice against lethal flu challenges, suggesting potential for broad-spectrum vaccines.
Area of Science:
- Vaccinology
- Virology
- Immunology
Background:
- Existing vaccines for influenza, SARS-CoV-2, RSV, and HIV are insufficient.
- Regulated microbes offer a novel platform for developing more effective vaccines.
Purpose of the Study:
- To review the development and vaccine potential of replication-competent controlled herpesviruses (RCCVs).
- To explore RCCVs as a novel vaccine platform.
Main Methods:
- Development and characterization of RCCVs.
- Assessment of RCCV replication control and immunogenicity in mice.
- Evaluation of RCCV-induced protection against influenza virus challenge.
Main Results:
- RCCVs can be activated for transient replication at the administration site, with no replication in the nervous system.
- RCCVs induced potent anti-herpetic immune responses in mice.
- Vaccination with RCCVs expressing influenza hemagglutinin provided broad protection against lethal influenza challenge, partly mediated by antibodies.
Conclusions:
- RCCVs represent a promising, controllable vaccine platform.
- RCCVs demonstrate potential for developing universal, non-seasonal vaccines against influenza.
- RCCVs may also be applicable to other rapidly evolving pathogens.
