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
. 2022 Nov:156:105273.
doi: 10.1016/j.jcv.2022.105273. Epub 2022 Aug 31.

Plaque-neutralizing antibody to BA.2.12.1, BA.4 and BA.5 in individuals with three doses of BioNTech or CoronaVac vaccines, natural infection and breakthrough infection

Samuel Sm Cheng  1 , Chris Kp Mok  2 , John Kc Li  1 , Susanna S Ng  3 , Bosco Hs Lam  4 , Trushar Jeevan  5 , Ahmed Kandeil  5 , Andrew Pekosz  6 , Karl Ck Chan  1 , Leo Ch Tsang  1 , Fanny W Ko  3 , Chunke Chen  2 , Karen Yiu  3 , Leo Lh Luk  1 , Ken Kp Chan  3 , Richard J Webby  5 , Leo Lm Poon  1 , David Sc Hui  7 , Malik Peiris  8
Affiliations

Plaque-neutralizing antibody to BA.2.12.1, BA.4 and BA.5 in individuals with three doses of BioNTech or CoronaVac vaccines, natural infection and breakthrough infection

Samuel Sm Cheng et al. J Clin Virol. 2022 Nov.

Abstract

Background: BA.2.12.1, BA.4 and BA.5 subvariants of SARS-CoV-2 variant-of-concern (VOC) Omicron (B.1.1.529) are spreading globally. They demonstrate higher transmissibility and immune escape.

Objectives: Determine BA.2.12.1, BA.4 and BA.5 virus plaque reduction neutralization test (PRNT) antibody titres in individuals recently vaccinated with BNT162b2 (n = 20) or CoronaVac (n = 20) vaccines or those convalescent from ancestral wild- type (WT) SARS-CoV-2 (n = 20) or BA.2 infections with (n = 17) or without (n = 7) prior vaccination.

Results: Relative to neutralization of the WT virus, those vaccinated with BNT162b2 had 4.8, 3.4, 4.6, 11.3 and 15.5-fold reductions of geometric mean antibody titres (GMT) to BA.1, BA.2, BA.2.12.1, BA.4 and BA.5 viruses, respectively. Similarly, those vaccinated with CoronaVac had 8.0, 7.0, 11.8, 12.0 and 12.0 fold GMT reductions and those with two doses of CoronaVac boosted by BNT162b2 had 6.1, 6.7, 6,3, 13.0 and 21.2 fold GMT reductions to these viruses, respectively. Vaccinated individuals with BA.2 breakthrough infections had higher GMT antibody levels vs. BA.4 (36.9) and BA.5 (36.9) than unvaccinated individuals with BA.2 infections (BA.4 GMT 8.2; BA.5 GMT 11.0).

Conclusions: BA.4 and BA.5 subvariants were less susceptible to BNT162b2 or CoronaVac vaccine elicited antibody neutralization than subvariants BA.1, BA.2 and BA.2.12.1. Nevertheless, three doses BNT162b2 or booster of BNT162b2 following two doses of CoronaVac elicited detectable BA.4 and BA.5 neutralizing antibody responses while those vaccinated with three doses of CoronaVac largely fail to do so. BA.2 infections in vaccinated individuals led to higher levels of BA.4 or BA.5 neutralizing antibody compared to those who were vaccine-naive.

Keywords: COVID-19; Omicron, Neutralization; SARS-CoV-2; Vaccine.

PubMed Disclaimer

Conflict of interest statement

Declaration of Competing Interest None of the authors had competing financial or non-financial interests.

Figures

Fig 1
Fig. 1
PRNT50 antibody titres to wild-type (WT) SARS-CoV-2 and Omicron subvariants BA.1, BA.2, BA.2.12.1, BA.4 and BA.5. A: Uninfected BNT162b2 individuals or CoronaVac vaccinated and non-vaccinated convalescent individuals from WT SARS-CoV-2 infection. GMTs to each virus in the same cohort are connected by lines. B: BA.2 infections in vaccinated (n = 17) and unvaccinated individuals (n = 7). GMTs in acute and convalescent stages were connected by lines. Comparison of antibody titres to different viruses was done using the Wilcoxon signed-rank test when comparing paired antibody titres to different viruses in the same serum and the two tailed Mann-Whitney U test when comparisons were made between different groups of individuals. The horizontal dotted line at a titre 1:25.6 represents the 50% protective titre against symptomatic infection and the shaded area represents the 95% confidence interval of this protective threshold (see results and reference for details).
See this image and copyright information in PMC

References

    1. Altarawneh H.N., Chemaitelly H., Ayoub H., Hasan M.R., Coyle P., Yassine H.M., Al Khatib H.A., Benslimane F., Al-Kanaani Z., Al Kuwari E., Jeremijenko A., Kaleeckal A.H., Latif A.N., Shaik R.M., Abdul Rahim H.F., Nasrallah G., Al Kuwari M.G., Butt A.A., Al Romaihi H.E., Al-Thani M.H., Al Khal A., Bertollini R., Tang P., Abu-Raddad L.J. Protection of SARS-CoV-2 natural infection against reinfection with the BA.4 or BA.5 Omicron subvariants. medRxiv. 2022 2022.2007.2011.22277448.
    1. Altarawneh H.N., Chemaitelly H., Ayoub H.H., Tang P., Hasan M.R., Yassine H.M., Al-Khatib H.A., Smatti M.K., Coyle P., Al-Kanaani Z., Al-Kuwari E., Jeremijenko A., Kaleeckal A.H., Latif A.N., Shaik R.M., Abdul-Rahim H.F., Nasrallah G.K., Al-Kuwari M.G., Butt A.A., Al-Romaihi H.E., Al-Thani M.H., Al-Khal A., Bertollini R., Abu-Raddad L.J. Effects of previous infection and vaccination on symptomatic omicron infections. N. Engl. J. Med. 2022;387(1):21–34. - PMC - PubMed
    1. Bowen J.E., Addetia A., Dang H.V., Stewart C., Brown J.T., Sharkey W.K., Sprouse K.R., Walls A.C., Mazzitelli I.G., Logue J.K., Franko N.M., Czudnochowski N., Powell A.E., Dellota E., Jr., Ahmed K., Ansari A.S., Cameroni E., Gori A., Bandera A., Posavad C.M., Dan J.M., Zhang Z., Weiskopf D., Sette A., Crotty S., Iqbal N.T., Corti D., Geffner J., Snell G., Grifantini R., Chu H.Y., Veesler D. Omicron spike function and neutralizing activity elicited by a comprehensive panel of vaccines. Science. 2022;377(6608):890–894. - PMC - PubMed
    1. Cao Y., Yisimayi A., Jian F., Song W., Xiao T., Wang L., Du S., Wang J., Li Q., Chen X., Yu Y., Wang P., Zhang Z., Liu P., An R., Hao X., Wang Y., Wang J., Feng R., Sun H., Zhao L., Zhang W., Zhao D., Zheng J., Yu L., Li C., Zhang N., Wang R., Niu X., Yang S., Song X., Chai Y., Hu Y., Shi Y., Zheng L., Li Z., Gu Q., Shao F., Huang W., Jin R., Shen Z., Wang Y., Wang X., Xiao J., Xie X.S. BA.2.12.1, BA.4 and BA.5 escape antibodies elicited by Omicron infection. Nature. 2022;608(7923):593–602. - PMC - PubMed
    1. Cele S., Jackson L., Khoury D.S., Khan K., Moyo-Gwete T., Tegally H., San J.E., Cromer D., Scheepers C., Amoako D.G., Karim F., Bernstein M., Lustig G., Archary D., Smith M., Ganga Y., Jule Z., Reedoy K., Hwa S.H., Giandhari J., Blackburn J.M., Gosnell B.I., Abdool Karim S.S., Hanekom W., von Gottberg A., Bhiman J.N., Lessells R.J., Moosa M.S., Davenport M.P., de Oliveira T., Moore P.L., Sigal A. Omicron extensively but incompletely escapes Pfizer BNT162b2 neutralization. Nature. 2022;602(7898):654–656. - PMC - PubMed

Publication types

Supplementary concepts