In the third year of the COVID-19 pandemic, the omicron variant of the novel coronavirus (SARS-CoV-2) has swept the world and spawned several other sub-variants. Currently, BA.2 is more popular in the world than BA.1. In addition, infections with the BA.2.12.1 variant are also increasing rapidly and have accounted for more than 50% of new infections in the United States. Therefore, the protective efficacy of existing vaccines and the need to develop future vaccination strategies are extremely important.
On July 6, 2022, the New England Journal (NEJM) published online the communication article of Institute of Microbiology, Chinese Academy of Sciences Academician Gao Fu’s team: Omicron SARS-CoV-2 Neutralization from Inactivated and ZF2001 Vaccines. The system evaluates the neutralizing effect of the new crown vaccine currently vaccinated in China and the booster shot against the new coronavirus and its Omicron variant.
In this study, researchers used pseudoviruses to neutralize to evaluate serum samples from vaccinated volunteers against the SARS-CoV-2 original strain and its various variants BA.1, BA.1.1, BA Neutralizing antibody titers of .2, BA.2.12.1, BA.3, BA.4 and BA.5. Vaccine recipients received three doses of one of the inactivated viral vaccines (CoronaVac and BBIBP-CorV) , the three-dose protein subunit vaccine ZF2001 (using dimeric RBD as the antigen), or two doses of inactivated CoronaVac Live vaccine followed by booster ZF2001.
In each vaccine group, neutralizing antibody titers against all tested variants were significantly lower than the corresponding titers against the original strain , indicating substantial immune evasion by the variants. Reduced neutralizing titers are associated with mutations in the spike protein.
BA.1.1 and BA.2 neutralized to a similar extent (within 1.5 times) as BA.1. BA.2.12.1 has an additional L452Q mutation in its RBD compared to BA.2 and therefore has a lower neutralizing titer of 1.4-1.7 times. In each vaccinated group, -neutralizing antibody titers against BA.4 and BA.5, which are currently dominant in South Africa, were 2.1-2.6 times lower than the BA.2 variant. status and may become the world’s next pandemic mutant strain. This finding suggests that two mutations (L452R and F486V) in the RBD cause antibodies elicited by current vaccines designed based on the sequence of the original strain to elicit less efficient compared to the RBD in the BA.2 subvariant .
To determine a better ZF2001 vaccination strategy, the researchers collected samples from volunteers 1 month after the third dose of the vaccine. subdivided this group into three subgroups based on the interval between the second and third dose: 1 month, 2 months and 4-6 months . In addition, to test the persistence of neutralizing antibodies in the long-interval subgroup after ZF2001 vaccination, the study obtained serum samples 4-7 months after the third dose.
The study found that neutralizing antibody titers increased with the interval between the second and third doses of , particularly against the Omicron variant. In vaccine volunteers who had an interval of 4-6 months between the second and third dose, neutralizing antibody titers were nearly 10 times higher than the original strain compared with the vaccine group where the interval between doses was 1 month. About 30 times higher for all variants. Vaccines in the long interval group were 100% seropositive against all Omicron tested. Neutralizing antibody titers and seroprevalence against all Omicron variants were higher in samples obtained 6 months after the last dose of vaccine in the long-interval subgroup than in the short-interval subgroup obtained 1 month after the last dose sample. The
heterologous boosted group had higher neutralizing antibody titers against the original strain and all groups than the group that received three doses of the same inactivated vaccine . However, compared with the response to the original strain, the response to BA.2, BA.2.12.1, BA.4 and BA.5 in the heterologous boosted group was reduced greater than that of the inactivated vaccine group. This finding suggests that these subvariants have more mutations in the RBD, leading to immune evasion. The rapid emergence of new variants of
makes the development of variant-specific vaccines difficult. The findings suggest that 's better immunization strategy against current vaccines may help improve neutralization levels of the Omicron variant. Since the ZF2001 vaccine consists of a protein subunit whose antigen is focused on the RBD, its use can induce increased neutralizing antibody titers against submicron variants through the administration of multiple booster doses and immune maturation methods. However, newer vaccines need to be developed as boosters to better protect against immune escape of current subvariants (especially BA.4 and BA.5) and possible future circulating subvariants.
Article link: DOI: 10.1056/NEJMc2206900
