Hidden variable models reveal the effects of infection from changes in host survival.

The impacts of disease on host vital rates can be demonstrated using longitudinal studies, but these studies can be expensive and logistically challenging. We examined the utility of hidden variable models to infer the individual effects of infectious disease from population-level measurements of survival when longitudinal studies are not possible. Our approach seeks to explain temporal deviations in population-level survival after introducing a disease causative agent when disease prevalence cannot be directly measured by coupling survival and epidemiological models. We tested this approach using an experimental host system (Drosophila melanogaster) with multiple distinct pathogens to validate the ability of the hidden variable model to infer per-capita disease rates. We then applied the approach to a disease outbreak in harbor seals (Phoca vituline) that had data on observed strandings but no epidemiological data. We found that our hidden variable modeling approach could successfully detect the per-capita effects of disease from monitored survival rates in both the experimental and wild populations. Our approach may prove useful for detecting epidemics from public health data in regions where standard surveillance techniques are not available and in the study of epidemics in wildlife populations, where longitudinal studies can be especially difficult to implement.

Using Dual Toll-like Receptor Agonism to Drive Th1-Biased Response in a Squalene- and α-Tocopherol-Containing Emulsion for a More Effective SARS-CoV-2 Vaccine.

A diversity of vaccines is necessary to reduce the mortality and morbidity of SARS-CoV-2. Vaccines must be efficacious, easy to manufacture, and stable within the existing cold chain to improve their availability around the world. Recombinant protein subunit vaccines adjuvanted with squalene-based emulsions such as AS03™ and MF59™ have a long and robust history of safe, efficacious use with straightforward production and distribution. Here, subunit vaccines were made with squalene-based emulsions containing novel, synthetic toll-like receptor (TLR) agonists, INI-2002 (TLR4 agonist) and INI-4001 (TLR7/8 agonist), using the recombinant receptor-binding domain (RBD) of SARS-CoV-2 S protein as an antigen. The addition of the TLR4 and TLR7/8 agonists, alone or in combination, maintained the formulation characteristics of squalene-based emulsions, including a sterile filterable droplet size (<220 nm), high homogeneity, and colloidal stability after months of storage at 4, 25, and 40 °C. Furthermore, the addition of the TLR agonists skewed the immune response from Th2 towards Th1 in immunized C57BL/6 mice, resulting in an increased production of IgG2c antibodies and a lower antigen-specific production of IL-5 with a higher production of IFNγ by lymphocytes. As such, incorporating TLR4 and TLR7/8 agonists into emulsions leveraged the desirable formulation and stability characteristics of emulsions and can induce Th1-type humoral and cell-mediated immune responses to combat the continued threat of SARS-CoV-2.