Göttingen Minipigs as a Model to Evaluate Longevity, Functionality, and Memory of Immune Response Induced by Pertussis Vaccines

Abstract

Evaluation of the short-term and long-term immunological responses in a preclinical model that simulates the targeted age population with a relevant vaccination schedule is essential for human vaccine development. A Göttingen minipig model was assessed, using pertussis vaccines, to demonstrate that vaccine antigen-specific humoral and cellular responses, including IgG titers, functional antibodies, Th polarization and memory B cells can be assessed in a longitudinal study. A vaccination schedule of priming with a whole cell (DTwP) or an acellular (DTaP) pertussis vaccine was applied in neonatal and infant minipigs followed by boosting with a Tdap acellular vaccine. Single cell RNAsequencing was used to explore the long-term maintenance of immune memory cells and their functionality for the first time in this animal model. DTaP but not DTwP vaccination induced pertussis toxin (PT) neutralizing antibodies. The cellular immune response was also characterized by a distinct Th polarization, with a Th-2-biased response for DTaP and a Th-1/Th-17-biased response for DTwP. No difference in the maintenance of pertussis-specific memory B cells was observed in DTaP- or DTwP-primed animals 6 months post Tdap boost. However, an increase in pertussis-specific T cells was still observed in DTaP primed minipigs, together with up-regulation of genes involved in antigen presentation and interferon pathways. Overall, the minipig model reproduced the humoral and cellular immune responses induced in humans by DTwP vs. DTaP priming, followed by Tdap boosting. Our data suggest that the Göttingen minipig is an attractive preclinical model to predict the long-term immunogenicity of human vaccines against Bordetella pertussis and potentially also vaccines against other pathogens.

Non-primate animal models for pertussis: back to the drawing board?

“…Transfer of maternal antibody during lactation and feeding of piglets has allowed for some study of passive mucosal immunity. The use of a unique pig model to study pertussis vaccinology has been proposed (Vaure et al 2021 ).…”

Long-Term Analysis of Pertussis Vaccine Immunity to Identify Potential Markers of Vaccine-Induced Memory Associated With Whole Cell But Not Acellular Pertussis Immunization in Mice

“…Unfortunately, baboons are not suitable for longevity studies because after 15 months of age they become resistant to infection [Tod Merkel, personal communication]. Other models of pertussis have been developed, including the rat model that allows for measurement of the hallmark cough of pertussis, and mini pigs that were recently used to study longevity of pertussis vaccines ( 33 , 34 ). While highly useful to study pertussis and vaccine-mediated responses, these models are still under-developed and suffer from the lack of broadly available tools and reagents.…”

Long-term analysis of pertussis vaccine immunity uncovers a memory B cell response to whole cell pertussis immunization that is absent from acellular immunized mice

“…Unfortunately, baboons are not suitable for longevity studies because after 15 months of age, they become resistant to infection (Tod Merkel; personal communication). Other models of pertussis have been developed, including the rat model that allows for measurement of the hallmark cough of pertussis, and mini pigs that were recently used to study longevity of pertussis vaccines 37,38 . While highly useful 5 to study pertussis and vaccine-mediated responses, these models are still underdeveloped and suffer from the lack of broadly available tools and reagents.…”