Abstract
The mass smallpox vaccination campaign has played a crucial role in smallpox eradication. Various strains of the vaccinia virus (VACV) were used as a live smallpox vaccine in different countries, their origin being unknown in most cases. The VACV strains differ in terms of pathogenicity exhibited upon inoculation of laboratory animals and reactogenicity exhibited upon vaccination of humans. Therefore, each generated strain or clonal variant of VACV needs to be thoroughly studied in in vivo systems. The clonal variant 14 of LIVP strain (LIVP-14) was the study object in this work. A comparative analysis of the virulence and immunogenicity of LIVP-14 inoculated intranasally (i.n.), intradermally (i.d.), or subcutaneously (s.c.) to BALB/c mice at doses of 108, 107, and 106 pfu was carried out. Adult mice exhibited the highest sensitivity to the i.n. administered LIVP-14 strain, although the infection was not lethal. The i.n. inoculated LIVP-14 replicated efficiently in the lungs. Furthermore, this virus was accumulated in the brain at relatively high concentrations. Significantly lower levels of LIVP-14 were detected in the liver, kidneys, and spleen of experimental animals. No clinical manifestations of the disease were observed after i.d. or s.c. injection of LIVP-14 to mice. After s.c. inoculation, the virus was detected only at the injection site, while it could disseminate to the liver and lungs when delivered via i.d. administration. A comparative analysis of the production of virus-specific antibodies by ELISA and PRNT revealed that the highest level of antibodies was induced in i.n. inoculated mice; a lower level of antibodies was observed after i.d. administration of the virus and the lowest level after s.c. injection. Even at the lowest studied dose (106 pfu), i.n. or i.d. administered LIVP-14 completely protected mice against infection with the cowpox virus at the lethal dose. Our findings imply that, according to the ratio between such characteristics as pathogenicity/immunogenicity/protectivity, i.d. injection is the optimal method of inoculation with the VACV LIVP-14 strain to ensure the safe formation of immune defense after vaccination against orthopoxviral infections.
Highlights
The declaration of global smallpox eradication was solemnly signed at the 33rd World HealthAssembly (WHA) on 8 May 1980 [1]
It was the first time in human history that a life-threatening viral disease claiming millions of lives every year was totally eradicated due to the efforts of physicians and scientists from many countries joined under the special World Health Organization (WHO)
Several vaccinia virus (VACV) strains, whose origin was not documented in most cases, were used as a live vaccine in different countries
Summary
(WHA) on 8 May 1980 [1] It was the first time in human history that a life-threatening viral disease claiming millions of lives every year was totally eradicated due to the efforts of physicians and scientists from many countries joined under the special World Health Organization (WHO) program [2,3]. Several vaccinia virus (VACV) strains, whose origin was not documented in most cases, were used as a live vaccine in different countries. These VACV strains differed in terms of pathogenicity (when used to infect various species of laboratory animals) and reactogenicity (when used for immunization of humans) [3,4,5,6]. A resolution strongly recommending the discontinuation of smallpox vaccination except for investigators at special risk was adopted by the
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