Thermostable Vaccines in Veterinary Medicine: State of the Art and Opportunities to Be Seized

Abstract

The COVID-19 pandemic has highlighted the weakness of the vaccine supply chain, and the lack of thermostable formulations is one of its major limitations. This study presents evidence from peer-reviewed literature on the development of thermostable vaccines for veterinary use. A systematic review and meta-analysis were performed to evaluate the immunogenicity and/or the efficacy/effectiveness of thermostable vaccines against infectious diseases. The selected studies (n = 78) assessed the vaccine's heat stability under different temperature conditions and over different periods. Only one study assessed the exposure of the vaccine to freezing temperatures. Two field studies provided robust evidence on the immunogenicity of commercial vaccines stored at temperatures far in excess of the manufacturer's recommended cold-chain conditions. The drying process was the most-used method to improve the vaccine's thermostability, along with the use of different stabilizers. The pooled vaccine efficacy was estimated to be high (VE = 69%), highlighting the importance of vaccination in reducing the economic losses due to the disease impact. These findings provide evidence on the needs and benefits of developing a portfolio of heat- and freeze-stable veterinary vaccines to unleash the true potential of immunization as an essential component of improved animal health and welfare, reduce the burden of certain zoonotic events and thus contribute to economic resilience worldwide.

Keywords: COVID-19 legacy; freeze-stable; heat-stable; thermostable; vaccine efficacy; vaccines.

Figure A1

The Baujat Plot of roe deer studies. Study number 5 [90] could be an outlier which may distort the effect size estimate, as well as its precision.

Figure A2

Influence analysis identifies study number 5 [90] as potential outlier.

Figure A3

Funnel plot of the meta-analysis on vaccines efficacy.

Figure 1

Diagram showing the stepwise process of study selection and pre-determined inclusion and reasons of exclusion for the broad search on thermostable vaccines (A), and the literature search on DNA vaccines (B).

Figure 2

Waffle graphs highlighting the attributes of the studies included: animal species (A), type of agent (B), country (C), and type of vaccine (D).

Figure 3

Forest plot of the risk ratio as a measure of vaccine efficacy (1-RR). Heterogeneity: I² = 95 (95% CI: 93–98), tau² = 0.44 (0.31–1.09), Q = 781.99, p-value < 0.0001.