A New Intranasal Influenza Vector-Based Vaccine TB/FLU-04L
                    Against Tuberculosis: Preclinical Safety Studies

Buzitskaya, Zhanna; Stosman, K. I.; Khairullin, Berik; Kassenov, Markhabat; Nurpeisova, Ainur; Sansyzbay, A. Abylai; Shurygina, Anna-Polina; Aleksandrov, Andrey G; Сивак, К. В.; Stukova, Marina

doi:10.1055/a-1785-3936

Cited by 15 publications

(11 citation statements)

References 8 publications

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“…The obtained vector demonstrated high replicative activity up to 8.0 lg TCID 50 /mL and was confirmed to be genetically stable after 15 consequent passages in Vero cells. The safety of TB/FLU-04L was proven in mice, guinea pigs, ferrets [ 38 ], and monkeys. There was no viral shedding detected in any animal model; the vaccine strain was completely attenuated in comparison with the wt A/PR/8/34 virus.…”

Section: Discussionmentioning

confidence: 99%

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Preclinical Evaluation of TB/FLU-04L—An Intranasal Influenza Vector-Based Boost Vaccine against Tuberculosis

Shurygina

Заболотных

Vinogradova

et al. 2023

IJMS

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Tuberculosis is a major global threat to human health. Since the widely used BCG vaccine is poorly effective in adults, there is a demand for the development of a new type of boost tuberculosis vaccine. We designed a novel intranasal tuberculosis vaccine candidate, TB/FLU-04L, which is based on an attenuated influenza A virus vector encoding two mycobacterium antigens, Ag85A and ESAT-6. As tuberculosis is an airborne disease, the ability to induce mucosal immunity is one of the potential advantages of influenza vectors. Sequences of ESAT-6 and Ag85A antigens were inserted into the NS1 open reading frame of the influenza A virus to replace the deleted carboxyl part of the NS1 protein. The vector expressing chimeric NS1 protein appeared to be genetically stable and replication-deficient in mice and non-human primates. Intranasal immunization of C57BL/6 mice or cynomolgus macaques with the TB/FLU-04L vaccine candidate induced Mtb-specific Th1 immune response. Single TB/FLU-04L immunization in mice showed commensurate levels of protection in comparison to BCG and significantly increased the protective effect of BCG when applied in a “prime-boost” scheme. Our findings show that intranasal immunization with the TB/FLU-04L vaccine, which carries two mycobacterium antigens, is safe, and induces a protective immune response against virulent M. tuberculosis.

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Section: Discussionmentioning

confidence: 99%

“…There was no viral shedding detected in any animal model; the vaccine strain was completely attenuated in comparison with the wt A/PR/8/34 virus. Toxicology studies revealed no toxicological or allergological effects of the vaccine [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

Preclinical Evaluation of TB/FLU-04L—An Intranasal Influenza Vector-Based Boost Vaccine against Tuberculosis

Shurygina

Заболотных

Vinogradova

et al. 2023

IJMS

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“…The WHO has issued recommendations that each country should develop its own vaccines and expand their vaccine production capacities. Over the past several years, the Scientific Research Institute for Biological Safety Problems (RIBSP) has been doing re-search to develop vaccines against influenza and M. tuberculosis for the Ministry of Health of the Republic of Kazakhstan [ 43 , 44 , 45 , 46 ]. Like many other countries, Kazakhstan started designing its own SARS-CoV-2 vaccine immediately after the COVID-19 outbreak with several candidate vaccines proposed by the RIBSP [ 47 , 48 , 49 , 50 ].…”

Section: Discussionmentioning

confidence: 99%

Pre-Clinical Safety and Immunogenicity Study of a Coronavirus Protein-Based Subunit Vaccine for COVID-19

Shorayeva,

Nakhanov,

Nurpeisova

et al. 2023

Vaccines

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Creating an effective and safe vaccine is critical to fighting the coronavirus infection successfully. Several types of COVID-19 vaccines exist, including inactivated, live attenuated, recombinant, synthetic peptide, virus-like particle-based, DNA and mRNA-based, and sub-unit vaccines containing purified immunogenic viral proteins. However, the scale and speed at which COVID-19 is spreading demonstrate a global public demand for an effective prophylaxis that must be supplied more. The developed products promise a bright future for SARS-CoV-2 prevention; however, evidence of safety and immunogenicity is mandatory before any vaccine can be produced. In this paper, we report on the results of our work examining the safety, toxicity, immunizing dose choice, and immunogenicity of QazCoVac-P, a Kazakhstan-made sub-unit vaccine for COVID-19. First, we looked into the product’s safety profile by assessing its pyrogenicity in vaccinated rabbit models and using the LAL (limulus amebocyte lysate) test. We examined the vaccine’s acute and sub-chronic toxicity on BALB/c mice and rats. The vaccine did not cause clinically significant toxicity-related changes or symptoms in our toxicity experiments. Finally, we performed a double immunization of mice, ferrets, Syrian hamsters, and rhesus macaques (Macaca mulatta). We used ELISA to measure antibody titers with the maximum mean geometric titer of antibodies in the animals’ blood sera totaling approximately 8 log2. The results of this and other studies warrant recommending the QazCoVac-P vaccine for clinical trials.

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“…Examples of T- cell stimulating adjuvants are AS01 E (adjuvant system 01 E ) and ISCOM (immune stimulating complex) based adjuvants ( 23 – 25 ). Alternatively, recombinant viral vectors expressing vaccine antigen(s) have been generated, which are mostly replication-deficient ( 27 – 31 ). The recently licensed Ebola vaccination scheme is based on a prime/boost scheme comprising adenovirus (Ad) 26 and Modified Vaccinia Ankara (MVA) virus as vectors, both expressing Ebola antigen ( 32 ).…”

Section: Major Vaccine Platformsmentioning

confidence: 99%

Vaccine development against tuberculosis before and after Covid-19

Kaufmann

2023

Front. Immunol.

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Coronavirus disease (Covid-19) has not only shaped awareness of the impact of infectious diseases on global health. It has also provided instructive lessons for better prevention strategies against new and current infectious diseases of major importance. Tuberculosis (TB) is a major current health threat caused by Mycobacterium tuberculosis (Mtb) which has claimed more lives than any other pathogen over the last few centuries. Hence, better intervention measures, notably novel vaccines, are urgently needed to accomplish the goal of the World Health Organization to end TB by 2030. This article describes how the research and development of TB vaccines can benefit from recent developments in the Covid-19 vaccine pipeline from research to clinical development and outlines how the field of TB research can pursue its own approaches. It begins with a brief discussion of major vaccine platforms in general terms followed by a short description of the most widely applied Covid-19 vaccines. Next, different vaccination regimes and particular hurdles for TB vaccine research and development are described. This specifically considers the complex immune mechanisms underlying protection and pathology in TB which involve innate as well as acquired immune mechanisms and strongly depend on fine tuning the response. A brief description of the TB vaccine candidates that have entered clinical trials follows. Finally, it discusses how experiences from Covid-19 vaccine research, development, and rollout can and have been applied to the TB vaccine pipeline, emphasizing similarities and dissimilarities.

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A New Intranasal Influenza Vector-Based Vaccine TB/FLU-04L Against Tuberculosis: Preclinical Safety Studies

Cited by 15 publications

References 8 publications

Preclinical Evaluation of TB/FLU-04L—An Intranasal Influenza Vector-Based Boost Vaccine against Tuberculosis

Preclinical Evaluation of TB/FLU-04L—An Intranasal Influenza Vector-Based Boost Vaccine against Tuberculosis

Pre-Clinical Safety and Immunogenicity Study of a Coronavirus Protein-Based Subunit Vaccine for COVID-19

Vaccine development against tuberculosis before and after Covid-19

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