The kinetics of IgG subclasses and contributions to neutralizing activity against SARS-CoV-2 wild-type strain and variants in healthy adults immunized with inactivated vaccine

Significance 

COVID-19 is a highly infectious disease caused by the SARS-CoV-2 virus, and it has had a devastating impact on individuals, communities, and countries worldwide. The virus can cause a range of symptoms, from mild to severe respiratory illness, and in some cases, it can lead to hospitalization and death. The virus has also had a significant impact on the global economy, education, and mental health. The COVID-19 pandemic has led to millions of deaths worldwide, and it has overwhelmed healthcare systems in many countries. The disease has a higher mortality rate among vulnerable populations, such as the elderly, those with underlying health conditions, and frontline workers. In addition to the direct impact of the disease, there have been many indirect consequences, such as disruptions in healthcare services, economic and social upheaval, and mental health consequences. However, the development and deployment of COVID-19 vaccines have been a crucial tool in the fight against the pandemic. Vaccines have been shown to be highly effective in preventing severe illness and death caused by COVID-19, and they have also been shown to reduce the transmission of the virus. The vaccines have undergone rigorous testing and have been shown to be safe and effective in clinical trials and real-world settings. The vaccination campaigns that have been carried out in many countries have contributed significantly to reducing the number of COVID-19 cases, hospitalizations, and deaths. The vaccines have also allowed many countries to reopen their economies, resume social activities, and restore a sense of normalcy. The vaccination campaigns are ongoing, and it is crucial that everyone who is eligible gets vaccinated to protect themselves and others and to help end the pandemic.

The vaccines developed to combat the SARS-CoV-2 virus have been shown to induce a robust immune response, particularly in the production of specific antibodies against the virus. Among these antibodies, the subclass of immunoglobulin G (IgG) is of particular interest due to its role in neutralizing the virus and providing protection against subsequent infections. Studies have shown that vaccination against SARS-CoV-2 leads to an increase in the production of IgG antibodies against the wild-type strain of the virus. Furthermore, different subclasses of IgG, such as IgG1, IgG2, IgG3, and IgG4, are also produced in response to vaccination. Neutralizing antibody, of which IgG is the primary component, is a crucial sign of vaccination effectiveness. There are four subtypes of IgG. Studies evaluating the humoral response to SARS-CoV-2 immunization have mostly measured total IgG up to this point, and the role of IgG subclasses is still unclear.

In a new study published in the journal Immunology, Beijing Center for Disease Prevention and Control investigators: Ms. Weixin Chen, Mr. Lichi Zhang, Dr. Juan Li, Ms. Shuang Bai, Ms. Yali Wang, Ms. Bing Zhang, Dr. Qun Zheng, Ms. Meng Chen, Dr. Wei Zhao, and Professor Jiang Wu examined the kinetics of IgG subclasses related to the wild-type SARS-CoV-2 RBD and looked into the relationship between IgG subclasses and neutralising ability. The study described the kinetics of neutralising antibodies against the wild-type SARS-CoV-2 and four variants (Beta, Gamma, Delta, and Omicron).

The research team elucidated the kinetics of neutralising antibodies against the wild-type strain and variations following a 2-dose primary vaccination and a booster dose of inactivated vaccine. According to the authors, IgG1 and IgG3 are the two IgG subtypes that are most prevalent. IgG1 levels were equivalent to IgG3 levels after primary vaccination, but IgG1 levels were significantly greater than IgG3 levels following booster immunisation. Interestingly, after 6 months following the initial vaccination, the GMT and seropositivity rate of the neutralising antibodies were greater than at 3 months. The researchers found that a higher percentage of people with more IgG1 antibodies than IgG3 antibodies had higher levels of neutralizing antibodies. They also suggested that the development of IgG1 antibodies may occur 3 to 6 months after receiving the SARS-CoV-2 vaccine. By grouping participants based on their neutralizing antibody levels, the researchers found a positive correlation between the ratio of IgG1 to IgG3 and the levels of neutralizing antibodies. This study highlights the importance of understanding the different types of antibodies and their roles in developing immunity to COVID-19.

Vccination against SARS-CoV-2 leads to the production of multiple subclasses of IgG, including IgG1, IgG2, IgG3, and IgG4. These antibodies play different roles in protecting against the virus, including neutralizing the virus, enhancing its uptake and destruction by immune cells, and regulating the immune response. In a nutshell, the scientists at Beijing Center for Disease Prevention and Control showed that the main COVID-19 inactivated vaccine vaccination achieved only poor neutralizing capacity after two doses. The ability to neutralize the wild-type strain and all variations considerably increased when the booster dose was administered. Neutralizing capacity was impacted by IgG subclass flipping in recipients of COVID-19 inactivated vaccines. The titer of the neutralizing antibody was strongly linked with the ratio of IgG1/IgG3. More study is necessary since the underlying process is not yet fully understood.

Reference

Chen W, Zhang L, Li J, Bai S, Wang Y, Zhang B, Zheng Q, Chen M, Zhao W, Wu J. The kinetics of IgG subclasses and contributions to neutralizing activity against SARSCoV2 wildtype strain and variants in healthy adults immunized with inactivated vaccine. Immunology. 2022;167(2):221-32.

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