3 RESULTS AND DISCUSSION
A total of 52 infected patients and 32 uninfected population participated in this study. Descriptive characteristics for the study population are presented in Table 1 and Table 2. We assayed the neutralizing activity against pangolin-CoV GX_P2V in serum samples obtained from 27 participants who had been vaccinated and boosted but recovered from SARS-CoV-2 BF.7 variant. Sera from patients who did not receive any vaccination but recovered from wild-type SARS-CoV-2 strain or Omicron infections, and sera from individuals who received two, three and four mixed vaccinations but had no history of SARS-CoV-2 infection, were used as controls. Sera from GX_P2V-infected golden hamsters were used as positive controls.
The geometric mean titers (GMTs) of neutralizing antibodies against GX_P2V in each group are presented in Table S1 and Figure 1B. Notably, regardless of the vaccine types, all vaccinated individuals who recovered from Omicron BF.7 infections had substantially higher GMTs of neutralizing antibodies against GX_P2V compared to cohorts of wild-type SARS-CoV-2 convalescents, uninfected two-dose vaccinees, uninfected three-dose vaccinees, uninfected four-mixed-dose vaccinees, and unvaccinated Omicron convalescents by factors of 45.3, 27.8, 60.3, 8.2, and 12.9, respectively (Figure 1B). Thus, Omicron breakthrough infections in wild-type SARS-CoV-2 vaccinees elicited superior cross-neutralizing antibodies against GX_P2V, a SARS-CoV-2 related virus.
Moreover, compared with unvaccinated individuals recovered from the Omicron BF.7 variant infection, the GMT was lower by a factor of 3.5, 2.2, 4.7 in wild-type SARS-CoV-2 convalescents, uninfected recipients of two-dose and three-dose inactivated vaccines, respectively. The GMT of uninfected participants but with four-mixed-dose vaccines was also higher by a factor of 5.5, 3.4, 7.3 than in wild-type SARS-CoV-2 convalescents, uninfected recipients of two-dose and three-dose inactivated vaccines, respectively. The results showed the effectiveness of mixed booster vaccinations and hybrid immunity protection against SARS-CoV-2-like virus infection.
In conclusion, our finding highlights the significance of prior vaccinations with wild-type SARS-CoV-2 vaccines in generating potent cross-protective immunity against breakthrough infections and supports reports of pan-SARS-CoV-2 neutralizing epitopes in the wild-type SARS-CoV-2 RBD.5,6 Additionally, our results further support GX_P2V as a promising live vaccine candidate against SARS-CoV-2.7 Overall, our study suggests that the general population in China has likely developed superior immunity to prevent future breaks of SARS-CoV-2-like viruses after the Omicron epidemic. Further research is necessary to corroborate these findings and to evaluate the long-term efficacy of such immunity in the population.