Comparison of the Effectiveness of Transepidemal and Intradermal Immunization of Mice with the Vacinia Virus

Abstract

The spread of the monkeypox virus infection among humans in many countries outside of Africa, which started in 2022, is now drawing the attention of the medical and scientific communities to the fact that immunization against this infection is sorely needed. According to current guidelines, immunization of people with the first-generation smallpox vaccine based on the vaccinia virus (VACV) LIVP strain, which is licensed in Russia, should be performed via transepidermal inoculation (skin scarification, s.s.). However, the long past experience of using this vaccination technique suggests that it does not ensure virus inoculation into patients skin with enough reliability. The procedure of intradermal (i.d.) injection of a vaccine can be an alternative to s.s. inoculation. The effectiveness of i.d. vaccination can depend on the virus injection site on the body. Therefore, the aim of this study was to compare the development of the humoral and cellular immune responses in BALB/c mice immunized with the LIVP VACV strain, which was administered either by s.s. inoculation or i.d. injection into the same tail region of the animal. A virus dose of 105 pfu was used in both cases. ELISA of serum samples revealed no significant difference in the dynamics and level of production of VACV-specific IgM and IgG after i.d. or s.s. vaccination. A ELISpot analysis of splenocytes from the vaccinated mice showed that i.d. administration of VACV LIVP to mice induces a significantly greater T-cell immune response compared to s.s. inoculation. In order to assess the protective potency, on day 45 post immunization, mice were intranasally infected with lethal doses of either the cowpox virus (CPXV) or the ectromelia virus (ECTV), which is evolutionarily distant from the VACV and CPXV. Both vaccination techniques ensured complete protection of mice against infection with the CPXV. However, when mice were infected with a highly virulent strain of ECTV, 50% survived in the i.d. immunized group, whereas only 17% survived in the s.s. immunized group. It appears, therefore, that i.d. injection of the VACV can elicit a more potent protective immunity against orthopoxviruses compared to the conventional s.s. technique.

Smallpox vaccination in a mouse model

“…Numerous studies have previously demonstrated that s.s. immunization with second-and fourth-generation VACVbased vaccines at doses of at least 10 5 -10 6 pfu fully protected mice against repeated lethal orthopoxvirus infection (Melamed et al, 2007;Jacobs et al, 2009;Shchelkunov et al, 2022a). * Statistically significant differences with p < 0.05.…”

“…In the case of i.d. injection, 20 µL of viral material (10 4 pfu) or normal saline (control group) was inoculated according to the procedure described earlier (Shchelkunov et al, 2022a). For s.s. immunization, 10 skin incisions were made using a 26G needle (0.45 × 16 mm) within the uppermost layer of epidermis.…”

“…On days 7, 14, 21, 28, 42, and 56 post inoculation (dpi) with the LIVP or LIVP-GFP viruses, blood samples were collected from the retro-orbital venous sinus in mice (six animals from each group) according to the procedure described previously (Shchelkunov et al, 2022a).…”

Comparison of the immunogenicity and protective efficacy of ACAM2000, MVA, and vectored subunit vaccines for Mpox in rhesus macaques

“…Limited MVA-BN vaccine supply led to US Food and Drug Administration recommendations to deliver an alternative regimen of one-fifth of the dose intradermally (ID) instead of a full dose subcutaneously (SC) (12). ID MVA immunization has been studied in mice, but little direct protection data are available for ID MVA vaccination against mpox in humans (12)(13)(14).…”