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
. 2021 Jul 22;13(8):1421.
doi: 10.3390/v13081421.

Elicitation of Broadly Neutralizing Antibodies against B.1.1.7, B.1.351, and B.1.617.1 SARS-CoV-2 Variants by Three Prototype Strain-Derived Recombinant Protein Vaccines

Yong Yang  1 , Jinkai Zang  1 , Shiqi Xu  1 , Xueyang Zhang  1 , Sule Yuan  1 , Haikun Wang  1 , Dimitri Lavillette  1 , Chao Zhang  1 , Zhong Huang  1
Affiliations

Elicitation of Broadly Neutralizing Antibodies against B.1.1.7, B.1.351, and B.1.617.1 SARS-CoV-2 Variants by Three Prototype Strain-Derived Recombinant Protein Vaccines

Yong Yang et al. Viruses. .

Abstract

The ongoing coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Most of the currently approved SARS-CoV-2 vaccines use the prototype strain-derived spike (S) protein or its receptor-binding domain (RBD) as the vaccine antigen. The emergence of several novel SARS-CoV-2 variants has raised concerns about potential immune escape. In this study, we performed an immunogenicity comparison of prototype strain-derived RBD, S1, and S ectodomain trimer (S-trimer) antigens and evaluated their induction of neutralizing antibodies against three circulating SARS-CoV-2 variants, including B.1.1.7, B.1.351, and B.1.617.1. We found that, at the same antigen dose, the RBD and S-trimer vaccines were more potent than the S1 vaccine in eliciting long-lasting, high-titer broadly neutralizing antibodies in mice. The RBD immune sera remained highly effective against the B.1.1.7, B.1.351, and B.1.617.1 variants despite the corresponding neutralizing titers decreasing by 1.2-, 2.8-, and 3.5-fold relative to that against the wild-type strain. Significantly, the S-trimer immune sera exhibited comparable neutralization potency (less than twofold variation in neutralizing GMTs) towards the prototype strain and all three variants tested. These findings provide valuable information for further development of recombinant protein-based SARS-CoV-2 vaccines and support the continued use of currently approved SARS-CoV-2 vaccines in the regions/countries where variant viruses circulate.

Keywords: COVID-19; S1; SARS-CoV-2 variants; neutralizing antibody; receptor binding domain; spike protein; vaccine.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Figure 1
Figure 1
Induction of broadly neutralizing antibodies against SARS-CoV-2 variants by recombinant RBD, S1, and S-trimer vaccines in mice. (A) SDS-PAGE and western blot (WB) analysis of purified RBD, S1, S-trimer antigens. An anti-RBD (inclusion bodies) polyclonal antibody was used as the detection antibody; (B) Mouse immunization and sampling schedule. Four groups of mice were immunized three times with either RBD/alum, S1/alum, S-trimer/alum, or PBS/alum; (C) S protein-specific serum antibody titers were determined by ELISA. Anti-PBS sera did not exhibit any binding at the lowest serum dilution (1:100) and was assigned a titer of 50 for calculation; (D) Neutralizing antibody titers of the antisera against wild-type SARS-CoV-2 pseudovirus. Anti-PBS sera did not exhibit any neutralization activity at the lowest serum dilution (1:400) and was assigned a titer of 200 for calculation. PVNT50, 50% pseudovirus neutralization titer. For panels (C,D), serum samples collected at weeks 18 and 32 were used; (E) Neutralizing antibody titers of the week-18 antisera against SARS-CoV-2 prototype, B.1.1.7, B.1.351, and B.1.617.1 pseudoviruses. Data of a given antiserum sample were linked to trace its neutralization titers against different pseudoviruses. For panels (C–E), each symbol represents one mouse. Geometric mean was calculated for each set of data, shown and compared. Statistical significance was determined by Student’s t-test and is indicated as follows: ns, not significant, * p < 0.05, ** p < 0.01. Error bars represent SD.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Zhou P., Yang X.L., Wang X.G., Hu B., Zhang L., Zhang W., Si H.R., Zhu Y., Li B., Huang C.L., et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579:270–273. doi: 10.1038/s41586-020-2012-7. - DOI - PMC - PubMed
    1. Zhu N., Zhang D.Y., Wang W.L., Li X.W., Yang B., Song J.D., Zhao X., Huang B.Y., Shi W.F., Lu R.J., et al. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N. Engl. J. Med. 2020;382:727–733. doi: 10.1056/NEJMoa2001017. - DOI - PMC - PubMed
    1. Sohrabi C., Alsafi Z., O’Neill N., Khan M., Kerwan A., Al-Jabir A., Iosifidis C., Agha R. World Health Organization declares global emergency: A review of the 2019 novel coronavirus (COVID-19) Int. J. Surg. 2020;76:71–76. doi: 10.1016/j.ijsu.2020.02.034. - DOI - PMC - PubMed
    1. Lan J., Ge J., Yu J., Shan S., Zhou H., Fan S., Zhang Q., Shi X., Wang Q., Zhang L., et al. Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor. Nature. 2020;581:215–220. doi: 10.1038/s41586-020-2180-5. - DOI - PubMed
    1. Xu C., Wang Y.X., Liu C.X., Zhang C., Han W.Y., Hong X.Y., Wang Y.F., Hong Q., Wang S.T., Zhao Q.Y., et al. Conformational dynamics of SARS-CoV-2 trimeric spike glycoprotein in complex with receptor ACE2 revealed by cryo-EM. Sci. Adv. 2021;7:eabe5575. doi: 10.1126/sciadv.abe5575. - DOI - PMC - PubMed

Publication types

MeSH terms