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Introduction to Vaccination
Published in Mesut Karahan, Synthetic Peptide Vaccine Models, 2021
Nezih Pişkinpaşa, Ömer Faruk Karasakal
In another study, it was found that MTBVAC, a live attenuated Mycobacterium tuberculosis strain against tuberculosis, can create trained immunity through induction of glycolysis and glutaminolysis and accumulate traces of histone methylation in its promoters. As a result, it provided a strong MTBVAC-induced heterologous protection against a fatal threat by Streptococcus pneumoniae in an experimental mouse pneumonia model (Tarancón et al. 2020). In one study, the protection of live attenuated BPZE1 vaccine against B. pertussis disease and the effectiveness of intra-nasal administration of this vaccine was studied. To examine the immune responses induced in humans (n = 12) receiving BPZE1, the magnitude of the antibody responses was studied and the resulting findings and the killing mechanisms induced by BPZE1 were found to have a high potential to improve vaccine efficacy and protection against B. pertussis transmission (Lin et al. 2020).
The future clinical implications of trained immunity
Published in Expert Review of Clinical Immunology, 2022
Valentin Nica, Radu A. Popp, Tania O. Crișan, Leo A. B. Joosten
The use of BCG as a vector for recombinant vaccines started over 30 years ago and has shown great promise in multiple studies. Its use presents high interest due to its good safety profile and low manufacturing cost. VPM1002 is a recombinant BCG vaccine obtained by replacing the C gene with hly, encoding listeriolysin. It is a potential candidate to replace its predecessor as an improvement, and is currently in a phase 3 clinical trial for Tuberculosis prevention in infants (NCT04351685). Another recombinant vaccine that presents high interest is MTBVAC, a live attenuated M. tuberculosis vaccine, obtained through deletion of the phoP and fadD26 genes. MTBVAC is also in phase 3 trials for TB treatment (NCT04975178), and initial studies suggest that it has a significantly higher efficacy compared to BCG [48]. When tested for TI effects, MTBVAC induced training in human monocytes, with higher pro-inflammatory cytokine release upon re-stimulation, metabolic reprogramming, H3K4me3 at TNFΑ and IL6 gene promoters, and in mouse models, cross-protection against S. pneumoniae was confirmed [49].
Advances and challenges in recombinant Mycobacterium bovis BCG-based HIV vaccine development: lessons learned
Published in Expert Review of Vaccines, 2018
Athina Kilpeläinen, Milena Maya-Hoyos, Narcís Saubí, Carlos Y. Soto, Joan Joseph
Many advances have been made in the rBCG:HIV vaccine field. However, overcoming immunodominance and eliciting strong functional immune responses is still a major challenge. As there still are no reliable correlates of protection to rely on when designing and evaluating HIV vaccines pre-clinically, hopefully, within five years we will have a better idea of exactly how to elicit an effective protective immune response against HIV. We will most probably have come a long way in improving the mycobacterial strains used, for instance shifting to the MTBVAC strain, the first live attenuated M. tuberculosis-based vaccine already tested in clinical trials. Recently, further development of the rBCG, AERAS-422, expressing mutant perfringolysin and overexpressing the TB antigens Ag85A, Ag85B, and Rv3407 was suspended due to Varicella-zoster virus activation in 2/8 recipients in a phase I clinical trial [163], demonstrating a need for improved safety. Furthermore, elucidation of the best combinations of promoters and expression systems, will allow us to achieve HIV-specific immune responses capable of targeting HIV without increasing acquisition, and reduce the risk of dissemination in HIV infected individuals. In addition, viral vectors and other means of boosting BCG prime immunizations will hopefully be improved, along with the HIV immunogens themselves. Finally, consortiums of different research groups working on HIV vaccines in different fields have been created, such as the European AIDS Vaccine Initiative 2020 which will broaden our knowledge and promote technology transfer in this field in a focused effort to develop protective and therapeutic HIV vaccines.