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Reconstructing the evolutionary origins of Mycobacterium tuberculosis, the causative agent of human tuberculosis, has helped identify bacterial factors that have led to the tubercle bacillus becoming such a formidable human pathogen. Here we report the discovery and detailed characterization of an exceedingly slow growing mycobacterium that is closely related to M. tuberculosis for which we have proposed the species name Mycobacterium spongiae sp. nov., (strain ID: FSD4b-SM). The bacterium was isolated from a marine sponge, taken from the waters of the Great Barrier Reef in Queensland, Australia. Comparative genomics revealed that, after the opportunistic human pathogen Mycobacterium decipiens, M. spongiae is the most closely related species to the M. tuberculosis complex reported to date, with 80% shared average nucleotide identity and extensive conservation of key M. tuberculosis virulence factors, including intact ESX secretion systems and associated effectors. Proteomic and lipidomic analyses showed that these conserved systems are functional in FSD4b-SM, but that it also produces cell wall lipids not previously reported in mycobacteria. We investigated the virulence potential of FSD4b-SM in mice and found that, while the bacteria persist in lungs for 56 days after intranasal infection, no overt pathology was detected. The similarities with M. tuberculosis, together with its lack of virulence, motivated us to investigate the potential of FSD4b-SM as a vaccine strain and as a genetic donor of the ESX-1 genetic locus to improve BCG immunogenicity. However, neither of these approaches resulted in superior protection against M. tuberculosis challenge compared to BCG vaccination alone. The discovery of M. spongiae adds to our understanding of the emergence of the M. tuberculosis complex and it will be another useful resource to refine our understanding of the factors that shaped the evolution and pathogenesis of M. tuberculosis. Author summary: Tuberculosis, caused by Mycobacterium tuberculosis, is still one of the world's deadliest infectious diseases. However, the origins and rise of M. tuberculosis as a successful pathogen are not well understood. Here, we report the isolation and characterisation of a marine sponge-derived mycobacterium (M. spongiae) from the Great Barrier Reef that has striking genotypic similarity to M. tuberculosis, with 80% average nucleotide identity. We further show by proteomic and lipidomic analyses that M. spongiae shares virulence factors and unique cell wall lipids with the tubercle bacillus. In spite of these conserved genotypic and phenotypic features, M. spongiae was not virulent in a mouse model of infection, leading us to investigate its potential as a vaccine strain or genetic donor for enhancing the current BCG vaccine for tuberculosis. Our findings contribute to understanding the evolutionary origins of M. tuberculosis and provide further insights into its pathogenesis. [ABSTRACT FROM AUTHOR]

Introduction: Persistent infections with the human papilloma viruses, HPV16 and HPV18, are associated with multiple cancers. Although prophylactic vaccines that induce HPV-neutralizing antibodies are effective against primary infections, they have no effect on HPV-mediated malignancies against which there is no approved immuno-therapy. Active research is ongoing in the immunotherapy of these cancers. Areas covered: In this review, we compared the preclinical efficacy of vaccine platforms used to treat HPV-induced tumors in the standard model of mice grafted with TC-1 cells, which express the HPV16 E6 and E7 oncoproteins. We searched for the key words, 'HPV,' 'vaccine,' 'therapy,' 'E7,' 'tumor,' 'T cells', and 'mice' for the period from 2005 to 2023 in PubMed and found 330 publications. Among them, we selected the most relevant to extract preclinical antitumor results to enable cross-sectional comparison of their efficacy. Expert opinion section: We compared these studies for HPV antigen design, immunization regimen, immunogenicity, and antitumor effect, considering their drawbacks and advantages. Among all strategies used in murine models, certain adjuvanted proteins and viral vectors showed the strongest antitumor effects, with the use of lentiviral vectors being the only approach to result in complete tumor eradication in 100% of experimental individuals while providing the longest-lasting memory. [ABSTRACT FROM AUTHOR]

Following the breakthrough of numerous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants in recent months and the incomplete efficiency of the currently available vaccines, development of more effective vaccines is desirable. Non-integrative, non-cytopathic and non-inflammatory lentiviral vectors elicit sterilizing prophylaxis against SARS-CoV-2 in preclinical animal models and are particularly suitable for mucosal vaccination, which is acknowledged as the most effective in reducing viral transmission. Here, we demonstrate that a single intranasal administration of a vaccinal lentiviral vector encoding a stabilized form of the original SARS-CoV-2 Spike glycoprotein induces full-lung protection of respiratory tracts and strongly reduces pulmonary inflammation in the susceptible Syrian golden hamster model against the prototype SARS-CoV-2. In addition, we show that a lentiviral vector encoding stabilized Spike of SARS-CoV-2 Beta variant (LV::SBeta-2P) prevents pathology and reduces infectious viral loads in lungs and nasal turbinates following inoculation with the SARS-CoV-2 Omicron variant. Importantly, an intranasal boost with LV::SBeta-2P improves cross-seroneutralization much better in LV::SBeta-2P-primed hamsters than in their counterparts primed with an LV-encoding Spike from the ancestral SARS-CoV-2. These results strongly suggest that an immune imprint with the original Spike sequence has a negative impact on cross-protection against new variants. Our results tackle the issue of vaccine effectiveness in people who have already been vaccinated and have vanished immunity and indicate the efficiency of LV-based intranasal vaccination, either as a single dose or as booster. [ABSTRACT FROM AUTHOR]