Minipigs as a neonatal animal model for tuberculosis vaccine efficacy testing

Neonatal and infant immunity for tuberculosis vaccine development: importance of age-matched animal models

“…Current data for CD8 + T cell response to BCG are limited, but our study found that the numbers of CD8 + T cells remained stable after both BCG vaccination and Mtb challenge. Our study also showed unexpected patterns of intracellular and extracellular expression of IFNγ by T cells early in life, which need to be investigated further (Ramos et al, 2019). Overall, no significant differences were observed in T cell phenotypes in response to BCG or Mtb challenge between unvaccinated and vaccinated piglets.…”

“…Our work demonstrated parallels between piglets and human infants vaccinated with BCG, indicating that future vaccine studies could benefit from using neonatal piglets prior to initiating clinical trials (Fig. 2) (Ramos et al, 2019).…”

“…We observed pathological changes, such as caseous necrosis and calcified lesions in the lungs and lymph nodes, recovered viable bacteria from both tissues, and demonstrated natural aerosol transmission from infected to uninfected pigs housed together (Ramos et al, 2017). Further, our group studied the immune response of neonatal piglets that were vaccinated with BCG at birth and challenged with MtB at 20 weeks of life (Ramos et al, 2019). At 4 weeks of life, naïve T cells predominated, and by 6 weeks of life, effector CD4 + T cells had taken over.…”

“…Today, only a few studies on TB vaccine development for children have used neonatal and young animal models; thus, here we review the contributions of mice, guinea pigs, rabbits, calves, goats, pigs and non-human primates (NHPs) as TB animal models, with special emphasis on neonatal immunity studies. We compare this information to a recent report from our group and others on the immune response to BCG in young miniature pigs, emphasizing the potential of the pig as a viable model for neonatal TB vaccine development (Lee et al, 2004;Ramos et al, 2019).…”

“…Whether this was induced by Mtb antigens, as found with other pathogens, or was an expected phenotype unique to pigs, remains unknown (Zuckermann, 1999). Further, BCG-vaccinated piglets had a higher number of activated monocytes at 4 and 6 weeks of life compared to unvaccinated piglets, and this trend continued as the piglets aged and after they received the Mtb challenge (Ramos et al, 2019). This active monocyte population could have been undergoing epigenetic reprogramming and trained immunity, a process that BCG induces in humans (Byrne et al, 2020).…”