AUTHOR=Jayaraman Swaminathan , Bauman Tyler , Maschhoff Amy , Shull Caleb , Li Peng , Magalhaes Edison , Trevisan Giovani , Linhares Daniel C. L. , Li Chunlin , Silva Gustavo S. TITLE=Causal inference study of PRRSV-MLV vaccine dosing effects on wean-to-finish performance during outbreaks JOURNAL=Frontiers in Veterinary Science VOLUME=Volume 12 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/veterinary-science/articles/10.3389/fvets.2025.1575029 DOI=10.3389/fvets.2025.1575029 ISSN=2297-1769 ABSTRACT=Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) greatly impacts swine production, and vaccination is the main method for reducing its economic effects on grow-finish populations. To cut costs, some producers use half-doses of modified live virus (MLV) vaccines, but the effectiveness of this approach during disease outbreaks is not well understood. This retrospective observational study used causal inference techniques to assess the impact of full-dose versus half-dose PRRSV-MLV vaccination on mortality and other key production outcomes in growing pigs experiencing PRRSV-2 outbreaks. Data analysis included 158 pig groups (47 nurseries, 111 finishing) from the Midwest United States that experienced PCR-confirmed PRRSV-2 outbreaks between 2021 and 2022, predominantly with L1C and L1A lineages. Mortality was established as the primary outcome, with cull rates, average daily gain, veterinary medicine costs, and percentage of grade A pigs at market as secondary outcomes. Using targeted maximum likelihood estimation (TMLE), a doubly robust causal inference technique, the study estimated the causal effects of vaccination dosage while accounting for potential confounders, including season, year, vaccine type, timing of vaccination, nursery stocking density, and presence of concurrent diseases. The analysis revealed distinct phase-specific effects: in the nursery, full-dose vaccination was associated with higher mortality difference (8.84, 95% CI: 4.7, 12.98) and increased veterinary costs (1.52 dollars/pig, 95% CI: 1.13, 1.91). However, in the finishing phase, full-dose vaccination significantly reduced the mortality difference (−3.40, 95% CI: −4.66, −2.29) despite slightly higher veterinary costs (0.47 dollars/pig, 95% CI: 0.03, 0.9). No significant differences between dosing strategies were observed in average daily gain, cull rates, or percentage of grade A pigs at the market. These findings suggest that while nursery groups vaccinated with full-dose had higher mortality and costs, it provided protective benefits during the economically critical finishing phase. For swine producers and veterinarians, these results indicate that the economic advantage of half-dose vaccination strategies should be carefully weighed against the increased mortality, particularly in systems with recurring PRRSV challenges. This study demonstrates the value of causal inference methods in analyzing real-world vaccination outcomes and provides evidence-based guidance for optimizing PRRSV vaccination protocols in commercial swine production.