# A Comparative Review of Veterinary and Human Vaccine Development Strategies: Insights into Herpesvirus Vaccinology from Latency to Elimination

## TL;DR

This paper compares vaccine strategies for herpesviruses in animals and humans, highlighting how veterinary approaches could improve human vaccine development.

## Contribution

The novel contribution is the comparative analysis of veterinary and human herpesvirus vaccine strategies, identifying shared challenges and potential cross-species solutions.

## Key findings

- Common technical bottlenecks include immune evasion mechanisms like MHC I downregulation and TAP inhibition.
- Veterinary 'Marker Vaccines' (DIVA strategies) show success but human HSV vaccine development remains stagnant.
- Promising solutions include T-cell epitope design and mucosal adjuvants to overcome latency and shedding issues.

## Abstract

Background: Members of the virus family Herpesviridae are among the most successful pathogen groups in evolutionary history. They not only pose a serious public health threat to humans but also cause significant economic losses in the global livestock industry. The primary immunological challenge in developing sterilizing vaccines is the lifelong latency of herpesviruses in the nervous system or lymphoid tissues. Methods: This analysis compares the vaccine strategies designed against the five most important Alphaherpesvirinae pathogens: HSV-1/2, PRV, BHV-1, EHV-1/4, and FHV-1. The contrast between the globally licensed veterinary vaccines and the relative stagnation in the field of human HSV vaccines is stark. However, there are notable success stories regarding the implementation of ‘Marker Vaccines’ (DIVA strategies) in veterinary medicine. This review examines various vaccine modalities, assessing their potential to mitigate clinical outbreaks and their shortcomings in preventing viral shedding and establishing latency. Results: This study reveals common technical bottlenecks across species, attributed to immune evasion mechanisms such as the downregulation of MHC I, TAP inhibition, the failure to induce robust mucosal IgA, and safety concerns regarding the recombination of live vectors. Conclusions: This review highlights several promising avenues that could lead to enhanced herpesvirus vaccines and recommends the rational design of T-cell epitopes alongside innovative mucosal adjuvants. Furthermore, it bridges the gap between veterinary and human vaccinology from a One Health perspective, suggesting that lessons learned from veterinary practices could facilitate necessary breakthroughs in human medicine.