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

Ramos, Laylaa; Lunney, Joan K.; Gonzalez-Juarrero, Mercedes

doi:10.1242/dmm.045740

Cited by 9 publications

(8 citation statements)

References 130 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Infant NHPs have been frequently used in studies to evaluate vaccines against Mycobacterium tuberculosis [229][230][231] and HIV [232][233][234]. Recently, Han et al used highthroughput technologies, including single-cell RNA sequencing of PBMCs, to perform an in-depth comparison of neonatal and adult immune responses to HIV immunization in macaques [235].…”

Section: Stepping Up Personalized Vaccinologymentioning

confidence: 99%

Predictive Markers of Immunogenicity and Efficacy for Human Vaccines

et al. 2021

View full text Add to dashboard Cite

Vaccines represent one of the major advances of modern medicine. Despite the many successes of vaccination, continuous efforts to design new vaccines are needed to fight “old” pandemics, such as tuberculosis and malaria, as well as emerging pathogens, such as Zika virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Vaccination aims at reaching sterilizing immunity, however assessing vaccine efficacy is still challenging and underscores the need for a better understanding of immune protective responses. Identifying reliable predictive markers of immunogenicity can help to select and develop promising vaccine candidates during early preclinical studies and can lead to improved, personalized, vaccination strategies. A systems biology approach is increasingly being adopted to address these major challenges using multiple high-dimensional technologies combined with in silico models. Although the goal is to develop predictive models of vaccine efficacy in humans, applying this approach to animal models empowers basic and translational vaccine research. In this review, we provide an overview of vaccine immune signatures in preclinical models, as well as in target human populations. We also discuss high-throughput technologies used to probe vaccine-induced responses, along with data analysis and computational methodologies applied to the predictive modeling of vaccine efficacy.

show abstract

Section: Stepping Up Personalized Vaccinologymentioning

confidence: 99%

Predictive Markers of Immunogenicity and Efficacy for Human Vaccines

et al. 2021

View full text Add to dashboard Cite

show abstract

“…The immune response and morphological characteristics of M. bovis granulomas have been studied mainly in cattle older than 6 months of age ( 4 ). However, very little information has been reported on the immunology of tuberculosis in young animals ( 17 ).…”

Section: Discussionmentioning

confidence: 99%

Mycobacterium bovis naturally infected calves present a higher bacterial load and proinflammatory response than adult cattle

Carrisoza‐Urbina¹,

Bedolla-Alva²,

Hernández-Pando³

et al. 2023

Front. Vet. Sci.

View full text Add to dashboard Cite

Granulomas are characteristic bovine tuberculosis lesions; studying this structure has improved our understanding of tuberculosis pathogenesis. However, the immune response that develops in granulomas of young cattle naturally infected with Mycobacterium bovis (M. bovis) has not been fully studied. Our previous work described an atypical pattern in granulomatous lesions of cattle younger than 4 months (calves) naturally infected previously M. bovis that did not correspond to the histological classification previously proposed. Histologically, granulomas from calves lack a connective tissue capsule and have fewer multinucleated giant cells (MGCs) and more acid-fast bacilli (AFB) than the classic tuberculosis lesions found in cattle older than 1 year (adults); this suggests a deficient immune response against M. bovis infection in young animals. Therefore, we used IHC and digital pathology analysis to characterize the in situ immune response of granulomas from young and adult cattle. The immunolabeling quantification showed that granulomas from calves had more mycobacteria, CD3+ cells, IFN-γ, TNF-α, and inducible nitric oxide synthase (iNOS) than those of adult cattle. Furthermore, calf granulomas showed lower immunolabeling of MAC387+, CD79+, and WC1+ cells without connective tissue surrounding the lesion and were associated with less vimentin, Alpha Smooth Muscle Actin (α-SMA), and TGF-β compared with granulomas from adult cattle. Our results suggest that the immune responses in granulomas of cattle naturally infected with M. bovis may be age dependent. This implies that an exacerbated proinflammatory response may be associated with active tuberculosis, producing more necrosis and a lower microbicidal capacity in the granulomas of calves naturally infected with M. bovis.

show abstract

“…Furthermore, BCG was shown to induce emergency granulopoiesis, possibly contributing to better immediate infection control ( 4 ). Despite the physiological similarity between pigs and humans ( 5 , 6 ), few studies have used the pig as a large animal model to unravel the immunological effects of BCG.…”

Section: Introductionmentioning

confidence: 99%

Immunogenicity of Bacillus Calmette-Guérin in pigs: potential as a translational model of non-specific effects of BCG

et al. 2023

View full text Add to dashboard Cite

BackgroundClinical and immunological studies in humans show that the live attenuated Bacillus Calmette-Guérin (BCG) vaccine has beneficial non-specific effects, increasing resistance against diseases other than tuberculosis. The underlying mechanisms are currently being explored. The pig exhibits considerable physiological similarity to humans in anatomy and physiology, suggesting that similar responses to BCG could be expected. Studies of the non-specific effects of BCG in pigs are scarce. We investigated the feasibility of using pigs as a large animal model to investigate the non-specific immunological effects of BCG.MethodsIn a series of experiments, we randomized newborn or young piglets from conventional farms to receiving BCG or placebo and investigated the persistence of live BCG bacteria in various tissues, the immunogenicity of BCG in ex vivo blood and in vitro stimulation assays, and the acute phase protein and clinical responses to heterologous infectious challenge with influenza A virus or Actinobacillus pleuropneumoniae.ResultsThe BCG vaccine was generally well tolerated. In contrast to humans, no skin reaction in the form of abscesses, ulcers, or scars was observed. Live BCG was recovered from draining lymph nodes in 2/13 animals 20 weeks after vaccination. Specific in vitro responses of IFN-γ to antigen-specific re-stimulation with mycobacterial antigen were increased but not TNF-responses to TLR2 or TLR4 agonists. A few genes were differentially expressed in blood after vaccination, including the antiviral genes RIG-I and CSF1, although the effect disappeared after correction for multiple testing. Clinical symptoms after heterologous bacterial or viral respiratory infections did not differ, nor did virus copies in nasopharyngeal samples after the challenge. However, the acute phase protein response was significantly reduced in BCG-vaccinated animals after influenza challenge but not after A. pleuropneumoniae challenge.DiscussionBCG was safe in pigs, inducing specific immunological responses, but our model did not corroborate the innate immunological responsiveness to BCG seen in humans. The dose of BCG or the bacterial and viral challenges may have been sub-optimal. Even so, the acute phase protein response to influenza infection was significantly reduced in BCG-vaccinated animals.

show abstract

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

Cited by 9 publications

References 130 publications

Predictive Markers of Immunogenicity and Efficacy for Human Vaccines

Predictive Markers of Immunogenicity and Efficacy for Human Vaccines

Mycobacterium bovis naturally infected calves present a higher bacterial load and proinflammatory response than adult cattle

Immunogenicity of Bacillus Calmette-Guérin in pigs: potential as a translational model of non-specific effects of BCG

Contact Info

Product

Resources

About