Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Nov 2;11(11):1677.
doi: 10.3390/vaccines11111677.

Cytokine and Chemokine Production in Mice Inoculated with NVX-CoV2373 (Nuvaxovid®) in Comparison with Omicron BA.4/5 Bivalent BNT162b2 (Comirnaty®)

Tetsuo Nakayama  1 , Takashi Ito  1   2 , Ryoka Ishiyama  3 , Kazuhiko Katayama  1
Affiliations

Cytokine and Chemokine Production in Mice Inoculated with NVX-CoV2373 (Nuvaxovid®) in Comparison with Omicron BA.4/5 Bivalent BNT162b2 (Comirnaty®)

Tetsuo Nakayama et al. Vaccines (Basel). .

Abstract

A recombinant SARS-CoV-2 spike protein vaccine (NVX-CoV2373) has been licensed and has a lesser incidence of adverse events. To know the immunological mechanisms of adverse events, the production of cytokines and chemokines was investigated in mice inoculated with NVX-CoV2373. Serum IL-6 was detected on Day 1 of the first and second doses and the IFN-γ, IL-4, IL-10, TNF-α, and IL-6 levels increased on Day 1 of the second dose at the inoculation site. The enhanced production of the inflammatory chemokines (CCL2), homeostatic chemokine (CXCL13), and Th2 chemokine (CCL17) was observed at the inoculation site on Day 1 of the second dose. These findings were compared with data obtained following inoculation with BNT162b2 bivalent vaccine containing omicron BA.4/5. Significantly lower levels of inflammatory chemokines were detected on Day 1 after the first dose of NVX-CoV2373 in sera and inoculation site than those following inoculation with bivalent BNT162b2 (p < 0.01), reflecting a lower incidence of adverse events after immunization with NVX-CoV2373 in humans. NVX-CoV2373 induced significantly higher concentrations of IFN-γ, TNF-α, and IL-10 at the inoculation site obtained on Day 1 of the second dose (p < 0.05). Significant higher levels of Th2 chemokines, CCL11 and CCL17, were induced at the inoculation site on Day 1 of the second dose (p < 0.01) and they explain the booster IgG EIA antibody response after the second dose of NVX-CoV2373.

Keywords: BNT162b2; NVX-CoV2373; adverse events; chemokine; cytokine.

PubMed Disclaimer

Conflict of interest statement

All authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Experimental schedule. Five-week-old female BALB/c mice were inoculated with 0.1 mL of NVX-CoV2373 at the left thigh. Serum and thigh muscle homogenate samples were obtained from three mice for each time point and after inoculation with bivalent BNT 162b2, serum and thigh muscle samples were obtained before injection and on Day 1 of first and second doses.
Figure 2
Figure 2
Cytokine profiles of IFN-γ, IL-4, and IL-6 following inoculation with NVX-CoV2373. IFN-γ, IL-4, and IL-6 production profiles in serum and thigh muscle homogenate samples are shown, representing Th1, Th2, and inflammatory cytokines. They are shown in box and whisker plots with median titers and the range of 5–95%.
Figure 3
Figure 3
Chemokine concentrations of CCL2, CXCL13, and CCL17 in serum and thigh muscle homogenate samples following inoculation with NVX-CoV2373. CCL2, CXCL13, and CCL17 are representative of inflammatory, homeostatic, and Th2 chemokines, respectively. They are shown in box and whisker plots with median titers and the range of 5–95%.
Figure 4
Figure 4
Comparison of IL-6, IFN-γ, TNF-α, IL-4, and IL-10 in serum and thigh muscle homogenates on Day 1 of the first and second doses following NVX-CoV2373 (Nuvaxovid®) and bivalent BNT162b2 (Comirnaty®). Cytokine concentrations are shown in box and whisker plots with median titers and the range of 5–95%: NVX-CoV2373 in blue columns (formula image: Nuvaxovid®) and orange columns (formula image: Comirnaty®). * p < 0.05.
Figure 5
Figure 5
Comparison of CCL2, CCL3, and CCL5 in serum and thigh muscle homogenates on Day 1 of the first and second doses following NVX-CoV2373 (Nuvaxovid®) and bivalent BNT162b2 (Comirnaty®). Chemokine concentrations are shown in box and whisker plots with median titers and the range of 5–95%: NVX-CoV2373 in blue columns (formula image: Nuvaxovid®) and orange columns (formula image: Comirnaty®). ** p < 0.01.
Figure 6
Figure 6
Comparison of CXCL13, CCL17 and CCL11 in serum and thigh muscle homogenates on Day 1 of the first and second doses following NVX-CoV2373 (Nuvaxovid®) and bivalent BNT162b2 (Comirnaty®). Chemokine concentrations are shown in box and whisker plots with median titers and the range of 5–95%: NVX-CoV2373 in blue columns (formula image: Nuvaxovid®) and orange columns (formula image: Comirnaty®). * p < 0.05, ** p < 0.01.
Figure 7
Figure 7
IgG EIA antibodies’ response against SARS-CoV-2 spike antigen following immunization with NVX-CoV2373 and BNT162b2 in a mouse model. Three mice were inoculated with NVX-CoV2373 and BNT162b2, and the second dose was given 4 weeks after the first dose. EIA titers are shown as the mean ± 1.0 SD of optical density.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Li Q., Guan X., Wu P., Wang X., Zhou L., Tong Y., Ren R., Leung K.S.M., Lau E.H.Y., Wong J.Y., et al. Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia. N. Engl. J. Med. 2020;382:1199–1207. doi: 10.1056/NEJMoa2001316. - DOI - PMC - PubMed
    1. Wu Z., McGoogan J.M. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China summary of a report of 72314 cases from the Chinese Center for Disease Control and Prevention. JAMA. 2020;323:1239–1242. doi: 10.1001/jama.2020.2648. - DOI - PubMed
    1. Corey L., Mascola J.R., Fauci A.S., Collins F.C. A strategic approach to COVID-19 vaccine R&D. Science. 2020;368:948–950. doi: 10.1126/science.abc5312. - DOI - PubMed
    1. Polack F.P., Thomas S.J., Kitchin N., Absalon J., Gurtman A., Lockhart S., Perez J.L., Marc G.P., Moreira E.D., Zerbini C., et al. Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine. N. Engl. J. Med. 2020;383:2603–2615. doi: 10.1056/NEJMoa2034577. - DOI - PMC - PubMed
    1. Baden L.R., El Sahly H.M., Essink B., Kotloff K., Frey S., Novak R., Diemert D., Spector S.A., Rouphael N., Creech B., et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N. Engl. J. Med. 2021;384:403–416. doi: 10.1056/NEJMoa2035389. - DOI - PMC - PubMed

LinkOut - more resources