Development of Human Vectored Brucellosis Vaccine Formulation: Assessment of Safety and Protectiveness of Influenza Viral Vectors Expressing Brucella Immunodominant Proteins in Mice and Guinea Pigs.

Dina Bugybayeva,Sholpan Ryskeldinova,Nurika Assanzhanova,Makhpal Sarmykova,Zhailaubay Kydyrbayev,Nadezhda Zinina,Kaissar Tabynov,Maxim Golovkin

doi:10.1155/2020/1438928

Dina Bugybayeva, Sholpan Ryskeldinova + Show 6 more

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https://doi.org/10.1155/2020/1438928

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Abstract

In this paper, we first used recombinant influenza viral vector (rIVV) subtype H5N1 expressing from the open reading frame of NS1 80 and NS1 124 amino acids of Brucella outer membrane proteins (Omp) 16 and 19, ribosomal L7/L12, and Cu-Zn superoxide dismutase (SOD) proteins to develop a human brucellosis vaccine. We made 18 combinations of IVVs in mono-, bi-, and tetravalent vaccine formulations and tested them on mice to select the safest and most effective vaccine samples. Then, the most effective vaccine candidates were further tested on guinea pigs. Safety of the rIVV-based vaccine candidate was evaluated by a mouse weight-gain test. Mice and guinea pigs were challenged with the virulent strain B. melitensis 16M. The protective effect of the rIVV-based vaccine candidate was assessed by quantitation of Brucella colonization in tissues and organs of challenged animals. All vaccine formulations were safe in mice. Tested vaccine formulations, as well as the commercial B. melitensis Rev.1 vaccine, have been found to protect mice from B. melitensis 16M infection within the range of 1.6 to 2.97 log10 units (P < 0.05). Tetravalent vaccine formulations from the position of NS1 80 amino acids (0.2 ± 0.4), as well as the commercial B. melitensis Rev.1 vaccine (1.2 ± 2.6), have been found to protect guinea pigs from B. melitensis 16M infection at a significant level (P < 0.05). Thus, tetravalent vaccine formulation Flu-NS1-80-Omp16+Flu-NS1-80-L7/L12+Flu-NS1-80-Omp19+Flu-NS1-80-SOD was chosen as a potential vaccine candidate for further development of an effective human vaccine against brucellosis. These results show a promising future for the development of a safe human vaccine against brucellosis based on rIVVs.

Highlights

Brucellosis is a zoonotic disease that is transmitted between species from animals to humans and is one of the most common infectious diseases in the world, with prevalence in developing countries
It was found that all vaccine samples, including B. melitensis Rev.1, were safe in mice after i.p. injection
In animals vaccinated with 80Omp16+L7/L12+Omp19+superoxide dismutase (SOD) (Figure 2(a), average value for the group: 0.01 log10 CFU/g of tissue) and 124-Omp16 +L7/L12+Omp19+SOD, we found a low degree of Brucella colonization in tissues in comparison with the PBS control group (2.9 log10 CFU/g of tissue)

Summary

Introduction

Brucellosis is a zoonotic disease that is transmitted between species from animals to humans and is one of the most common infectious diseases in the world, with prevalence in developing countries. Vector-based systems on the platform of attenuated viruses (Semliki Forest virus) or bacteria (Ochrobactrum anthropi, Yersinia enterocolitica, and Escherichia coli) have been developed and tested as vaccine candidates against brucellosis, including the presenting recombinant of Brucella proteins as Cu-Zn SOD, L7/L12, and Omp19 [14,15,16,17,18,19,20,21]. These vector platforms were tested predominantly in mouse models and induced vigorous Th1-type immune responses. In the majority of studies, protection was not confirmed against a challenge with virulent bacterial strain

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