The rapid development of safe and effective COVID-19 vaccines was once thought to be the beginning of the end of the pandemic.
1However, with the decline of vaccine efficacy and the emergence of variants of concern (VOCs), massive breakthrough infections have occurred in vaccinated populations.
- Sharma O.
- Sultan A.A.
- Ding H.
- Triggle C.R.
A review of the progress and challenges of developing a vaccine for COVID-19.
Front Immunol. 2020; 11585354
- Alcendor D.J.
- Matthews-Juarez P.
- Smoot D.
- Hildreth J.E.K.
- Lamar K.
- Tabatabai M.
- et al.
Breakthrough COVID-19 Infections in the US: implications for prolonging the pandemic.
Vaccines (Basel). 2022; 10
3Recent articles in this journal mentioned that breakthrough infections caused by VOCs can induce higher immune responses than original infections and simple vaccination.
- Gupta R.K.
- Topol E.J.
COVID-19 vaccine breakthrough infections.
Science. 2021; 374: 1561-1562
- Yadav P.D.
- Sapkal G.N.
- Sahay R.R.
- Patil D.Y.
- Deshpande G.R.
- Jain R.
- et al.
Elevated neutralization of Omicron with sera of COVID-19 recovered and breakthrough cases vaccinated with Covaxin than two dose naive vaccinees.
J Infect. 2022; 84: 834-872
5The evaluation of neutralization capacity against omicron induced by the “hybrid immunity” elicited by different vaccines and infections is crucial to the future vaccination strategy and the development of new vaccines.
- YangYang G.X.
- Yang L.
- Li J.
- Zhang J.
- Wei L.
- et al.
Regular and booster vaccination with inactivated vaccines enhance the neutralizing activity against Omicron variant both in the breakthrough infections and vaccinees.
J Infect. 2022; 84: 579-613
In this study, we recruited 60 participants from 3 locally clustered COVID-19 outbreaks in Rizhao, Jinan, and Weihai, Shandong Province, China in October 2021, May and June 2022. They were all confirmed cases of COVID-19 with positive PCR tests, and the SARS-CoV-2 sequence of most participants has been confirmed by whole genome sequencing on Miseq. We examined neutralizing activity against the wild-type SARS-CoV-2 and omicron BA.2.3 sub-variant from convalescent individuals with AY.126, P.1.15 or BA.2 breakthrough infections through live virus neutralization assay. The indirect ELISA kit (Vazyme, China) based on spike protein were used to quantify S-binding IgG antibodies against SARS-CoV-2. The design of this study and the spike protein mutations of the VOCs involved are shown in Fig. 1A-B. See supplementary materials for detailed participant characteristics and methods.
Notably, the neutralization ability against BA.2.3 of all breakthrough infection patients was 3.18–8 times lower than wild-type. In breakthrough infections following two doses of vaccine, the geometric mean titre (GMT) against wild-type and BA.2.3 in the 6 individuals who breakthrough by AY.126 were 3.32-times(from 1952.12 to 587.37) and 2.62-times(from 232.59 to 88.61) higher than individuals with BA.2 breakthrough infections; 3 patients who breakthrough by P.1.15 had 1.58-times(from 930.37 to 587.37) and 3.31-times(from 293.05 to 88.61) higher GMT than individuals who breakthrough by BA.2 (Fig. 2A). After three doses of the inactivated vaccine, patients with P.1.15 breakthrough infection also had a 1.83-times(from 1254.14 to 686.06) and 1.37-times(from 156.77 to 114.07) higher titre against wild-type and BA.2.3 compared with individuals who breakthrough by BA.2 (Fig. 2B).
Among the 13 P1.15-infected patients, 10 patients received three doses of vaccine had 1.35-times(from 1254.14 to 930.37) higher titre against wild-type than patients who received two doses, but no improvement for BA.2.3 (Fig. 2C). Of the 41 BA.2-infected patients, 5 unvaccinated patients didn't develop high neutralizing antibodies by virtue of only once infection. For individuals with inactivated vaccines, the GMT against wild-type and BA.2.3 increased from 256.00, 41.93 to 686.06, 114.07, respectively, with the increase of pre-infection doses. In patients who vaccinated with three doses, the ZF2001 vaccine induced 1.45-times(from 991.79 to 686.06) and 1.64-times(from 187.04 to 114.07) higher titre against wild-type and BA.2.3 than the inactivated vaccine (Fig. 2D).
The change trend of S-binding IgG antibody level in each group was similar to that of neutralizing antibody. The correlation results between neutralizing titers against wild-type SARS-CoV-2, and BA.2.3, and S-binding IgG titer were R = 0.64 (p < 0.0001), R = 0.54 (p < 0.0001), and R = 0.54 (p < 0.0001), and showing a moderate significant positive correlation between antibodies(Figure S1–2). Similar to a recent study,
6we also found that the ELISA assays could reflect the humoral immune response partly.
- Ferre V.M.
- Lebourgeois S.
- Chenane H.R.
- Menidjel R.
- Masson C.
- Collin G.
- et al.
Vaccine Ab neutralization against Omicron and SARS-CoV-2 variants using neutralization and specific ELISA assays.
J Infect. 2022; 84: 834-872
Consistent with previous studies,
- Dejnirattisai W.
- Huo J.
- Zhou D.
- Zahradnik J.
- Supasa P.
- Liu C.
- et al.
SARS-CoV-2 Omicron-B.1.1.529 leads to widespread escape from neutralizing antibody responses.
Cell. 2022; 185 (467-84 e15)
8the immune evasion ability of the omicron shouldn't be underestimated. Under the same vaccination conditions, the resistance to wild-type and BA.2.3 after BA.2 breakthrough infection was weaker than that of AY.126 and P.1.15 breakthrough infection. It suggests that the heterologous “hybrid immunity” could mediate stronger humoral immunity, whereas the omicron variant is less immunogenic in comparison.
- Cao Y.
- Wang J.
- Jian F.
- Xiao T.
- Song W.
- Yisimayi A.
- et al.
Omicron escapes the majority of existing SARS-CoV-2 neutralizing antibodies.
Nature. 2022; 602: 657-663
9Although breakthrough infections may still occur after vaccination, vaccinated individuals could trigger stronger immune recall after infection than unvaccinated individuals.
- Servellita V.
- Syed A.M.
- Morris M.K.
- Brazer N.
- Saldhi P.
- Garcia-Knight M.
- et al.
Neutralizing immunity in vaccine breakthrough infections from the SARS-CoV-2 Omicron and Delta variants.
Cell. 2022; 185 (1539-48 e5)
10A limitation of this study is based on a small number of individuals. But this real-world antibody results from breakthrough infections individuals suggest that implementing complete vaccinations, optimizing vaccination and developing new vaccines regimens the key to combating VOCs and reducing the incidence of COVID-19.
- Richardson S.I.
- Madzorera V.S.
- Spencer H.
- Manamela N.P.
- van der Mescht M.A.
- Lambson B.E.
- et al.
SARS-CoV-2 Omicron triggers cross-reactive neutralization and Fc effector functions in previously vaccinated, but not unvaccinated, individuals.
Cell Host Microbe. 2022; 30 (880-6 e4)
This work was supported by the Major Scientific and Technological Innovation Project in Shandong Province (grant numbers: 2020SFXGFY02–1), Key Research and Development plan of Shandong Province (grant numbers: 2021RZA01021) and Natural Science Foundation of Shandong Province(grant numbers: ZR202112040005).
Declaration of Competing Interest
The authors have declared that no conflicts of interest exist.
Appendix. Supplementary materials
- A review of the progress and challenges of developing a vaccine for COVID-19.Front Immunol. 2020; 11585354
- Breakthrough COVID-19 Infections in the US: implications for prolonging the pandemic.Vaccines (Basel). 2022; 10
- COVID-19 vaccine breakthrough infections.Science. 2021; 374: 1561-1562
- Elevated neutralization of Omicron with sera of COVID-19 recovered and breakthrough cases vaccinated with Covaxin than two dose naive vaccinees.J Infect. 2022; 84: 834-872
- Regular and booster vaccination with inactivated vaccines enhance the neutralizing activity against Omicron variant both in the breakthrough infections and vaccinees.J Infect. 2022; 84: 579-613
- Vaccine Ab neutralization against Omicron and SARS-CoV-2 variants using neutralization and specific ELISA assays.J Infect. 2022; 84: 834-872
- SARS-CoV-2 Omicron-B.1.1.529 leads to widespread escape from neutralizing antibody responses.Cell. 2022; 185 (467-84 e15)
- Omicron escapes the majority of existing SARS-CoV-2 neutralizing antibodies.Nature. 2022; 602: 657-663
- Neutralizing immunity in vaccine breakthrough infections from the SARS-CoV-2 Omicron and Delta variants.Cell. 2022; 185 (1539-48 e5)
- SARS-CoV-2 Omicron triggers cross-reactive neutralization and Fc effector functions in previously vaccinated, but not unvaccinated, individuals.Cell Host Microbe. 2022; 30 (880-6 e4)
Published online: October 20, 2022
Accepted: October 16, 2022
© 2022 The British Infection Association. Published by Elsevier Ltd. All rights reserved.