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. 2025 Feb 14:12:1543398.
doi: 10.3389/fmed.2025.1543398. eCollection 2025.

Safety and immunogenicity of Ad5-nCoV administered intradermally by needle-free injector in rats

Li Chen #  1   2 , Xiaoyin Zhang #  3 , Lairun Jin  1 , Lihua Hou  4 , Fengcai Zhu  1   2 , Jingxin Li  1   2
Affiliations

Safety and immunogenicity of Ad5-nCoV administered intradermally by needle-free injector in rats

Li Chen et al. Front Med (Lausanne). .

Abstract

Objectives: To evaluate the safety and immunogenicity of adenovirus type 5 vectored COVID-19 vaccine (Ad5-nCoV), by intradermal immunization with a needle-free injector in rats.

Methods: This study was divided into two parts. In study A, 105 rats were randomly assigned to seven groups, to receive the low-dose, medium-dose, or high-dose vaccine by needle-free intradermal injections (NFI), or needle-based intramuscular injections (NI), or needle-free intradermal injections with saline solution as a control group. Blood samples were collected on day 0 before vaccination, and day 7, day 14, day 21 and day 28 after vaccination. Binding antibody, pseudovirus neutralizing antibody as well as cellular immune response were measured. The safety endpoints included weight changes and skin reactions. In study B, 32 rats were randomly assigned to four groups to receive low-dose, or medium-dose vaccine by NFI or NI, to observe pathological changes at the injection site following immunization.

Results: No safety concern was noted associated with NFI of Ad5-nCoV. Comparable levels of neutralizing antibodies against various variants induced by NFI compared to NI at the same dosage.

Conclusion: The NFI immunization would be considered as an alternative immunization method to replace the traditional NI for the Ad5-nCoV.

Keywords: COVID-19; adenovirus type-5 vector-based COVID-19 vaccine; immunogenicity; needle-free injector; safety.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Trend of body weight change, erythema and eschar formation and edema formation in rats. Error bars are 95% CIs. Panel (a) is trend of body weight change 28 days after vaccination. Panel (b) shows changes in the number of erythema and eschar formation 7 days after vaccination. Panel (c) shows changes in the number of edema formation 7 days after vaccination.
Figure 2
Figure 2
Skin and muscle histopathological examination. *The black arrows indicate mild to moderate local subcutaneous hemorrhage in the interstitium. The red arrows denote the formation of crusts in the epidermal cornified layer, with localized connective tissue proliferation visible in the dermis. The blue arrows signify mild inflammatory cell infiltration in the interstitium. Due to the equivalence in the dosage of the single-point injection between the high-dose group and the medium-dose group, the pathological changes in the skin and muscle were solely analyzed in the low and medium-dose groups.
Figure 3
Figure 3
Pseudovirus neutralizing antibody levels against the wild-type strain, Delta subvariant and Omicron BA.4/5 subvariant. Error bars are 95% CIs. The horizontal dotted lines denote the cutoff levels for detection. *p < 0.05, **p < 0.01, ***p < 0.001. Panel (a) is pseudovirus neutralizing antibody levels against the wild-type strain. Panel (b) is pseudovirus neutralizing antibody levels against the Delta subvariant. Panel (c) is pseudovirus neutralizing antibody levels against the Omicron BA.4/5 subvariant.
Figure 4
Figure 4
The IFN-γ-secreting cells per million cells on day 28 post-immunization. Error bars indicate median and quartiles of IFN-γ-secreting cells per million cells for each group; scatter points indicate IFN-γ-secreting cells per million cells for each sample.
See this image and copyright information in PMC

References

    1. Nantanee R, Aikphaibul P, Jaru-Ampornpan P, Sodsai P, Himananto O, Theerawit T, et al. . Immunogenicity and reactogenicity after booster dose with AZD1222 via intradermal route among adult who had received CoronaVac. Vaccine. (2022) 40:3320–9. doi: 10.1016/j.vaccine.2022.04.067, PMID: - DOI - PMC - PubMed
    1. Tawinprai K, Siripongboonsitti T, Porntharukchareon T, Wittayasak K, Thonwirak N, Soonklang K, et al. . Immunogenicity and safety of an intradermal fractional third dose of ChAdOx1 nCoV-19/AZD1222 vaccine compared with those of a standard intramuscular third dose in volunteers who previously received two doses of CoronaVac: a randomized controlled trial. Vaccine. (2022) 40:1761–7. doi: 10.1016/j.vaccine.2022.02.019, PMID: - DOI - PMC - PubMed
    1. Lambert PH, Laurent PE. Intradermal vaccine delivery: will new delivery systems transform vaccine administration? Vaccine. (2008) 26:3197–208. doi: 10.1016/j.vaccine.2008.03.095, PMID: - DOI - PubMed
    1. Gockel C. Transcutaneous immunization induces mucosal and systemic immunity: a potent method for targeting immunity to the female reproductive tract. Mol Immunol. (2000) 37:537–44. doi: 10.1016/S0161-5890(00)00074-2 - DOI - PubMed
    1. Stoitzner P, Holzmann S, McLellan AD, Ivarsson L, Stössel H, Kapp M, et al. . Visualization and characterization of migratory Langerhans cells in murine skin and lymph nodes by antibodies against Langerin/CD207. J Invest Dermatol. (2003) 120:266–74. doi: 10.1046/j.1523-1747.2003.12042.x, PMID: - DOI - PubMed

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