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To the Editor: The coronavirus disease 2019 (Covid-19) pandemic is still ongoing,1 and the B.1.1.529 (or omicron) variant, first detected in November 2021, has already spread globally. The ability of the omicron variant to escape vaccine-elicited immunity is of great concern. Inactivated vaccines, such as CoronaVac and BBIBP-CorV, and protein subunit vaccines, such as ZF2001, have been widely used in China and several other countries.2 We analyzed the binding and neutralizing antibodies elicited by three doses (two priming doses and one booster dose) of an inactivated vaccine or ZF2001, as well as those in persons who had recovered from Covid-19 (the convalescent group). The serum samples from the ZF2001 recipients were grouped according to the interval between the second and third dose; the persons in the short-interval ZF2001 group had received the second priming dose 1 month after the first dose and then the third dose 1 month after the second dose, and those in the prolonged-interval ZF2001 group had received the second priming dose 1 month after the first dose and then the third dose 4 months after the second dose. The decreases in the titers of antibodies binding to the omicron variant were greater in the serum samples from both ZF2001 groups than in those from the inactivated-vaccine group or the convalescent group (Figure 1A through 1D and Table S1 in the Supplementary Appendix, available with the full text of this letter at NEJM.org).

ases in the titers of antibodies binding to the omicron variant were greater in the serum samples from both ZF2001 groups than in those from the inactivated-vaccine group or the convalescent group (Figure 1A through 1D and Table S1 in the Supplementary Appendix, available with the full text of this letter at NEJM.org). We used a pseudovirus system to test the serum samples for neutralizing antibodies against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) prototype strain and variants of concern, including the omicron variant. In the convalescent group, 15 of 16 serum samples were shown to be negative for neutralizing antibodies against the omicron variant, which indicates that the immune escape potential of this variant is high — a finding consistent with those of other recent analyses.3 However, the antibodies in the serum samples from the inactivated-vaccine and ZF2001 groups remained effective in the neutralization of the omicron variant with relatively high seroconversion. Among the persons who received three doses of either vaccine, 10 of 16 samples (62%) in the inactivated-vaccine group, 9 of 16 samples (56%) in the short-interval ZF2001 group, and 16 of 16 samples (100%) in the prolonged-interval ZF2001 group were shown to be positive for neutralizing antibodies against the omicron variant. In a fifth group of persons who also had a prolonged 4-month interval between the second and third dose of ZF2001 but whose serum samples were collected 4 to 6 months after the third dose, 9 of 13 serum samples (69%) were positive for neutralizing antibodies against the omicron variant. The titer of neutralizing antibodies against the omicron variant was lower than that against the prototype SARS-CoV-2 strain by a factor of 17.4 in the convalescent group, by a factor of 5.1 in the inactivated-vaccine group, by a factor of 10.6 in the short-interval ZF2001 group, and by a factor of 3.1 in the prolonged-interval ZF2001 group (Figure 1F through 1J). Moreover, as we reported previously,4 a longer interval between the second priming dose of vaccine and the booster dose appears to result in higher neutralizing antibody titers against all variants tested.

short-interval ZF2001 group, and by a factor of 3.1 in the prolonged-interval ZF2001 group (Figure 1F through 1J). Moreover, as we reported previously,4 a longer interval between the second priming dose of vaccine and the booster dose appears to result in higher neutralizing antibody titers against all variants tested. These findings support the use of multiple vaccine boosts and prolonged intervals between vaccine doses to protect against highly mutated variants such as omicron in persons who had previously received two priming doses of vaccine or who had previously recovered from SARS-CoV-2. Our results are in accordance with those of previous studies involving messenger RNA vaccine recipients.5 Next-generation vaccines that stimulate broad protection against SARS-CoV-2 variants are also needed.