Journal of Infectious Diseases & Therapy
Open Access

Coronavirus disease (COVID-19) vaccines usually could induce acceptable neutralizing antibody response at first two weeks, and the neutralizing antibody level would gradually decline to undetected level within 6 months [1]. Guidelines from World Health Organization and U.S. Centers for Disease Control and Prevention encouraged booster immunization in adults, but did not recommend it for minors due to the lack of relevant data [2, 3]. This commentary focused on the insights and findings of heterologous booster vaccination with one dose of recombinant COVID-19 vaccine (ZF2001) in children aged 3 to 17 years who had received two doses of inactivated vaccines.Coronavirus disease (COVID-19) vaccines usually could induce acceptable neutralizing antibody response at first two weeks, and the neutralizing antibody level would gradually decline to undetected level within 6 months [1]. Guidelines from World Health Organization and U.S. Centers for Disease Control and Prevention encouraged booster immunization in adults, but did not recommend it for minors due to the lack of relevant data [2, 3]. This commentary focused on the insights and findings of heterologous booster vaccination with one dose of recombinant COVID-19 vaccine (ZF2001) in children aged 3 to 17 years who had received two doses of inactivated vaccines.

First, an important finding was that a booster schedule in minors could induce robust immune responses and provide a certain degree of cross-protection against Omicron variants. Some other studies also certified it [4, 5]. This finding was significant to minors for improving the immune persistence and the resistance to new variants. Booster immunization could also produce immune responses in minors with Inborn Errors of Immunity (IEIs) [6]. One study showed that the neutralizing antibodies and T-cell responses in adolescents were noninferior to those in adults and another study indicated that minors could produce more robust immune response than adults after booster immunization [7, 8], although there were some limitations for this comparison, such as the level of antibody before booster immunization, the difference on laboratory selections or detection methods in different studies.

Second, we found that heterologous booster immunization resulted in better levels of neutralizing antibodies than homologous booster immunization in minors. And it was adherence to the result of another study, which indicated that homologous booster immunization induced less immune response than heterologous booster immunization with adenovirus vector vaccine in children aged 6-17 years who had received two doses of inactivated vaccine [5]. These results were similar to trial in adults and it might be attributed to the recall of memory B cells and the de novo activation of B cells [9, 10].

Finally, heterologous booster immunization with one dose of ZF2001 in minors showed a satisfactory safety profile and there was no significant difference for overall safety results between homologous boost and heterologous boost of recombinant protein vaccine in minors [4]. The heterologous booster dose did not significantly increase the risk of adverse reactions. However, under intramuscular injection, the incidence of adverse reactions of viral vector vaccine was higher than that of inactivated vaccine in minors when applied as heterologous booster [5]. Similar trends have been observed in studies involving adults, in which the incidence of adverse reactions of viral vector and mRNA vaccines was slightly higher than recombinant protein vaccines as heterologous booster doses [11,12].

Could booster immunization programs in minors improve neutralizing antibody levels? The answer is yes. The ideas and findings of this article were significant for improving the persistence of immunity in minors and preventing emerging variants infections. This would help to expand the application of booster immunization strategy and provide reference for the development of related immunization strategies.

1. Jia Z, Wang K, Xie M, Wu J, Hu Y, et al. (2024) A third dose of inactivated vaccine augments the potency, breadth, and duration of anamnestic responses against SARS-CoV-2. Protein Cell 27:pwae033.

   [Crossref] [Google Scholar] [PubMed]

2. World Health Organization (2021) Interim statement on COVID-19 vaccine booster doses.
3. Centers for Disease Control and Prevention (2021) CDC statement on ACIP booster recommendations.
4. Wang L, Wu Z, Ying Z, Li M, Hu Y, et al. (2022) Safety and immunogenicity following a homologous booster dose of CoronaVac in children and adolescents. Nat Commun 13:6952.

   [Crossref] [Google Scholar] [PubMed]

5. Huang T, Zhang S, Dai DF, Wang BS, Zhuang L, et al. (2023) Safety and immunogenicity of heterologous boosting with orally aerosolised or intramuscular Ad5-nCoV vaccine and homologous boosting with inactivated vaccines (BBIBP-CorV or CoronaVac) in children and adolescents: A randomised, open-label, parallel-controlled, non-inferiority, single-centre study. Lancet Respir Med 11:698-708.

   [Crossref] [Google Scholar] [PubMed]

6. Leung D, Mu X, Duque JSR, Cheng SMS, Wang M, et al. (2022) Safety and immunogenicity of 3 doses of BNT162b2 and CoronaVac in children and adults with inborn errors of immunity. Front Immunol 13:982155.

   [Crossref] [Google Scholar] [PubMed]

7. Cao Y, Hao X, Wang X, Wu Q, Song R, et al. (2022) Humoral immunogenicity and reactogenicity of CoronaVac or ZF2001 booster after two doses of inactivated vaccine. Cell Res 32:107-109.

   [Crossref] [Google Scholar] [PubMed]

8. Mu X, Cohen CA, Leung D, Rosa Duque JS, Cheng SMS, et al. (2022) Antibody and T cell responses against wild-type and Omicron SARS-CoV-2 after third-dose BNT162b2 in adolescents. Signal Transduct Target Ther 7:397.

   [Crossref] [Google Scholar] [PubMed]

9. Ai J, Zhang H, Zhang Q, Zhang Y, Lin K, et al. (2022) Recombinant protein subunit vaccine booster following two-dose inactivated vaccines dramatically enhanced anti-RBD responses and neutralizing titers against SARS-CoV-2 and variants of concern. Cell Res 2022, 32(1):103-106.

   [Crossref] [Google Scholar] [PubMed]

10. Ai J, Guo J, Zhang H, Zhang Y, Yang H, et al. (2022) Cellular basis of enhanced humoral immunity to SARS-CoV-2 upon homologous or heterologous booster vaccination analyzed by single-cell immune profiling. Cell Discov 8:114.

    [Crossref] [Google Scholar]

11. Liu X, Li Y, Wang Z, Cao S, Huang W, et al. (2022) Safety and superior immunogenicity of heterologous boosting with an RBD-based SARS-CoV-2 mRNA vaccine in Chinese adults. Cell Res 32:777-780.

    [Crossref] [Google Scholar] [PubMed]

12. Li J, Hou L, Guo X, Jin P, Wu S, et al. (2022) Heterologous AD5-nCOV plus CoronaVac versus homologous CoronaVac vaccination: A randomized phase 4 trial. Nat Med 28:401-409.  

    [Crossref] [Google Scholar] [PubMed]