Research Advances for Virus-vectored Tuberculosis Vaccines and Latest Findings on Tuberculosis Vaccine Development

Abstract

Tuberculosis (TB), caused by respiratory infection with Mycobacterium tuberculosis, remains a major global health threat. The only licensed TB vaccine, the one-hundred-year-old Bacille Calmette-Guérin has variable efficacy and often provides poor protection against adult pulmonary TB, the transmissible form of the disease. Thus, the lack of an optimal TB vaccine is one of the key barriers to TB control. Recently, the development of highly efficacious COVID-19 vaccines within one year accelerated the vaccine development process in human use, with the notable example of mRNA vaccines and adenovirus-vectored vaccines, and increased the public acceptance of the concept of the controlled human challenge model. In the TB vaccine field, recent progress also facilitated the deployment of an effective TB vaccine. In this review, we provide an update on the current virus-vectored TB vaccine pipeline and summarize the latest findings that might facilitate TB vaccine development. In detail, on the one hand, we provide a systematic literature review of the virus-vectored TB vaccines are in clinical trials, and other promising candidate vaccines at an earlier stage of development are being evaluated in preclinical animal models. These research sharply increase the likelihood of finding a more effective TB vaccine in the near future. On the other hand, we provide an update on the latest tools and concept that facilitating TB vaccine research development. We propose that a pre-requisite for successful development may be a better understanding of both the lung-resident memory T cell-mediated mucosal immunity and the trained immunity of phagocytic cells. Such knowledge could reveal novel targets and result in the innovative vaccine designs that may be needed for a quantum leap forward in vaccine efficacy. We also summarized the research on controlled human infection and ultra-low-dose aerosol infection murine models, which may provide more realistic assessments of vaccine utility at earlier stages. In addition, we believe that the success in the ongoing efforts to identify correlates of protection would be a game-changer for streamlining the triage of multiple next-generation TB vaccine candidates. Thus, with more advanced knowledge of TB vaccine research, we remain hopeful that a more effective TB vaccine will eventually be developed in the near future.

The Induction of Antigen 85B-Specific CD8+ T Cells by Recombinant BCG Protects against Mycobacterial Infection in Mice

“…For example, MVA85A is a recombinant viral vector-based vaccine that expresses the Mtb immunodominant antigen Ag85A and was the first of the new TB vaccines to complete phase IIb clinical trials [ 15 ]. In addition to the MVA85A vaccine, various viral vector-based vaccines have been developed [ 16 ].…”

Proteome Profile Changes Induced by Heterologous Overexpression of Mycobacterium tuberculosis-Derived Antigens PstS-1 (Rv0934) and Ag85B (Rv1886c) in Mycobacterium microti

“…Our work focused on the genetic engineering of mycobacterial strains belonging to the Mtb complex to produce antigens of interest. Such antigens and their epitopes, either alone or in combination, may help to develop new ways to increase the efficacy of current TB vaccines, for example, the currently available M. bovis BCG live-attenuated vaccine [ 68 , 69 , 70 , 71 , 72 ]. Therefore, we generated and analyzed two recombinant strains of M. microti overexpressing the M. tuberculosis PstS-1 and Ag85B antigens.…”

Treatments of Mycobacterium tuberculosis and Toxoplasma gondii with Selenium Nanoparticles

“…The requisite clinical trials will take another 10 years to complete, even if a correlate of protection is found and a good vaccine formulation is found. As a result, by 2022, it will be impossible to anticipate a vaccination [ 84 ].…”

“…Seroprevalence is higher in several Latin American nations, including Argentina, Brazil, Cuba, Jamaica, and Venezuela (51–72%), as well as West African countries along the Gulf of Guinea, such as Benin, Cameroon, Congo, Gabon, and Togo (54–77%) [ 137 , 138 ]. Women of childbirth age in Southeast Asia, China, and Korea had lower seroprevalences (4–39%) [ 84 , 136 ]. Seroprevalences are also low in cold-climate areas, such as the Scandinavian countries (11–28%) [ 136 , 139 ].…”