Humoral and Cellular Immune Responses Induced by 3a DNA Vaccines Against Severe Acute Respiratory Syndrome (SARS) or SARS-like Coronavirus in Mice

Overview

Journal Clin Vaccine Immunol

Publisher American Society for Microbiology

Specialties Allergy & Immunology
Pathology

Date 2008 Nov 7

PMID 18987164

Citations 18

Authors

Baojing Lu

Ling Tao

Ting Wang

Zhenhua Zheng

Bao Li

Ze Chen

Yi Huang

Qinxue Hu

Hanzhong Wang

Affiliations

Soon will be listed here.

Abstract

Vaccine development for severe acute respiratory syndrome coronavirus (SARS-CoV) has mainly focused on the spike (S) protein. However, the variation of the S gene between viruses may affect the efficacy of a vaccine, particularly for cross-protection against SARS-like CoV (SL-CoV). Recently, a more conserved group-specific open reading frame (ORF), the 3a gene, was found in both SARS-CoV and SL-CoV. Here, we studied the immunogenicity of human SARS-CoV 3a and bat SL-CoV 3a DNA vaccines in mice through electroporation immunization followed by enzyme-linked immunosorbent, enzyme-linked immunospot, and flow cytometry assays. Our results showed that high levels of specific humoral responses were induced by SARS-CoV 3a and SL-CoV 3a DNA vaccines. Furthermore, a strong Th1-based cellular immune response was stimulated by both DNA vaccines. The vaccines stimulated gamma interferon production mainly by CD8(+) T cells and interleukin-2 (IL-2) mainly by CD4(+) T cells. Of interest, the frequency of IL-2-positive cells elicited by the SARS-CoV 3a DNA vaccine was significantly higher than that elicited by the SL-CoV 3a DNA vaccine. In summary, our study provides a reference for designing cross-protective DNA vaccines based on the group-specific ORFs of CoVs.

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References

Li W, Shi Z, Yu M, Ren W, Smith C, Epstein J . Bats are natural reservoirs of SARS-like coronaviruses. Science. 2005; 310(5748):676-9. DOI: 10.1126/science.1118391. View

Kong W, Xu L, Stadler K, Ulmer J, Abrignani S, Rappuoli R . Modulation of the immune response to the severe acute respiratory syndrome spike glycoprotein by gene-based and inactivated virus immunization. J Virol. 2005; 79(22):13915-23. PMC: 1280202. DOI: 10.1128/JVI.79.22.13915-13923.2005. View

Zhong X, Guo Z, Yang H, Peng L, Xie Y, Wong T . Amino terminus of the SARS coronavirus protein 3a elicits strong, potentially protective humoral responses in infected patients. J Gen Virol. 2006; 87(Pt 2):369-373. DOI: 10.1099/vir.0.81078-0. View

Huang J, Ma R, Wu C . Immunization with SARS-CoV S DNA vaccine generates memory CD4+ and CD8+ T cell immune responses. Vaccine. 2006; 24(23):4905-13. PMC: 7115633. DOI: 10.1016/j.vaccine.2006.03.058. View

Akerstrom S, Tan Y, Mirazimi A . Amino acids 15-28 in the ectodomain of SARS coronavirus 3a protein induces neutralizing antibodies. FEBS Lett. 2006; 580(16):3799-803. PMC: 7094653. DOI: 10.1016/j.febslet.2006.06.002. View

Lu W, Zheng B, Xu K, Schwarz W, Du L, Wong C . Severe acute respiratory syndrome-associated coronavirus 3a protein forms an ion channel and modulates virus release. Proc Natl Acad Sci U S A. 2006; 103(33):12540-5. PMC: 1567914. DOI: 10.1073/pnas.0605402103. View

Akerstrom S, Mirazimi A, Tan Y . Inhibition of SARS-CoV replication cycle by small interference RNAs silencing specific SARS proteins, 7a/7b, 3a/3b and S. Antiviral Res. 2006; 73(3):219-27. PMC: 7114101. DOI: 10.1016/j.antiviral.2006.10.008. View

Bai B, Lu X, Meng J, Hu Q, Mao P, Lu B . Vaccination of mice with recombinant baculovirus expressing spike or nucleocapsid protein of SARS-like coronavirus generates humoral and cellular immune responses. Mol Immunol. 2007; 45(4):868-75. PMC: 7112626. DOI: 10.1016/j.molimm.2007.08.010. View

Harty J, Tvinnereim A, White D . CD8+ T cell effector mechanisms in resistance to infection. Annu Rev Immunol. 2000; 18:275-308. DOI: 10.1146/annurev.immunol.18.1.275. View

10.

Kelly E, Won A, Refaeli Y, Van Parijs L . IL-2 and related cytokines can promote T cell survival by activating AKT. J Immunol. 2002; 168(2):597-603. DOI: 10.4049/jimmunol.168.2.597. View

11.

Wu C, Kirman J, Rotte M, Davey D, Perfetto S, Rhee E . Distinct lineages of T(H)1 cells have differential capacities for memory cell generation in vivo. Nat Immunol. 2002; 3(9):852-8. DOI: 10.1038/ni832. View

12.

Bourgeois C, Veiga-Fernandes H, Joret A, Rocha B, Tanchot C . CD8 lethargy in the absence of CD4 help. Eur J Immunol. 2002; 32(8):2199-207. DOI: 10.1002/1521-4141(200208)32:8<2199::AID-IMMU2199>3.0.CO;2-L. View

13.

Bourgeois C, Rocha B, Tanchot C . A role for CD40 expression on CD8+ T cells in the generation of CD8+ T cell memory. Science. 2002; 297(5589):2060-3. DOI: 10.1126/science.1072615. View

14.

Peiris J, Lai S, Poon L, Guan Y, Yam L, Lim W . Coronavirus as a possible cause of severe acute respiratory syndrome. Lancet. 2003; 361(9366):1319-25. PMC: 7112372. DOI: 10.1016/s0140-6736(03)13077-2. View

15.

Drosten C, Gunther S, Preiser W, van der Werf S, Brodt H, Becker S . Identification of a novel coronavirus in patients with severe acute respiratory syndrome. N Engl J Med. 2003; 348(20):1967-76. DOI: 10.1056/NEJMoa030747. View

16.

Marra M, Jones S, Astell C, Holt R, Brooks-Wilson A, Butterfield Y . The Genome sequence of the SARS-associated coronavirus. Science. 2003; 300(5624):1399-404. DOI: 10.1126/science.1085953. View

17.

Yang Z, Kong W, Huang Y, Roberts A, Murphy B, Subbarao K . A DNA vaccine induces SARS coronavirus neutralization and protective immunity in mice. Nature. 2004; 428(6982):561-4. PMC: 7095382. DOI: 10.1038/nature02463. View

18.

Tan Y, Teng E, Shen S, Tan T, Goh P, Fielding B . A novel severe acute respiratory syndrome coronavirus protein, U274, is transported to the cell surface and undergoes endocytosis. J Virol. 2004; 78(13):6723-34. PMC: 421683. DOI: 10.1128/JVI.78.13.6723-6734.2004. View

19.

Mosmann T, Coffman R . TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol. 1989; 7:145-73. DOI: 10.1146/annurev.iy.07.040189.001045. View

20.

Bottomly K . A functional dichotomy in CD4+ T lymphocytes. Immunol Today. 1988; 9(9):268-74. DOI: 10.1016/0167-5699(88)91308-4. View