Recently, the team of Academician Yang Zhenglin of Sichuan Provincial People's Hospital and Jinfeng Laboratory of Sichuan Academy of Medical Sciences published a research paper titled "Dynamics of neutralizing antibodies against COVID-19 Omicron subvariants following breakthrough infection in southwest China between December 2022 and April 2024" in the international journal Signal Transduction and Targeted Therapy.

From December 2022 to January 2023, the SARS-CoV-2 Omicron BA.5/BF.7 variant was rapidly exerted in mainland China, causing tens of millions of breakthrough infections. Although most patients have mild symptoms and can recover from outpatient or home treatment, some cases still progress to severe illness and even death. This peak of infection is not only a challenge to the medical system, but also an important moment to evaluate the establishment of an immune barrier in the population. Neutralizing antibody (Nab) titers serve as an important indicator of individual and herd immunity, and changes during this period reflect the complex interactions between vaccine-induced immunity, viral mutation, and antibody decay.

In order to deeply analyze the response patterns of the immune system after breakthrough infection, the research team launched a 16-month longitudinal cohort study in southwestern China, covering December 2022 to April 2024, and a total of 3,128 serum samples were collected. The study conducted quantitative detection of neutralizing antibody levels against variant strains such as BA.5, XBB.1.5, EG.5 and JN.1, and recorded the subject's vaccination background, age and gender information. The study established a complete immunoevolution curve by calculating geometric mean titers (GMTs) and comparing antibody levels changes between different time points and strains.

The main research found that 1. Vaccinated patients have stronger immune activation after infection: In the early stages of the BA.5 epidemic in December 2022, the antibody titers of unvaccinated patients were extremely low (GMT <25), while those with two/three doses of vaccinated patients were significantly higher than those of other groups after infection, suggesting that vaccine-induced memory B cells are rapidly activated after breaking through infection. 2. Antibody levels will decline rapidly over time: January 2023 is the peak period for antibody levels, and thereafter it will show a monthly downward trend. The rate of neutralization ability decline synchronizes with the strain mutation, which means that the herd immunity barrier is extremely vulnerable to new strains. 3. Emerging mutant strains show increasing immune escape ability: XBB.1.5 (Spring 2023) triggers partial reinfection, with moderate antibody titers ； EG.5 (Summer 2023) rekindles some immunity in groups with declining antibody levels ； JN.1 (early 2024) has the lowest neutralization titer, indicating that it has the strongest immune escape and is also one of the most popular strains in the world during this period. 4. There is a certain degree of cross-immune response: With the succession of the mutant strain, the study found that the antibody levels of the population to EG.5 and XBB.1.5 also increased simultaneously during the JN.1 epidemic, indicating that multiple viral exposures can promote partial broad-spectrum immunity. 5. The influence of age and gender factors is limited: There is no significant correlation between age and neutralizing antibody titers, suggesting that age is not the main influence factor in this cohort. ； Except for BA.5, the antibody titers of the other variants had no significant correlation with age. Women performed stronger in their immune response to BA.5, consistent with the trend of "higher levels of women's antibodies" in previous studies, but this effect is very limited. 6. The antibody fluctuation cycle is highly consistent with the small-scale infection wave: the fluctuation of antibody titers shows a small-cycle pattern every 4-7 months, which appears simultaneously with multiple small-scale infection peaks (May, August, and November 2023), indicating that the immune barrier is susceptible to the dual influence of time and mutant pressure.

This study not only supplements real-world medium- and long-term immunization data, but also verifies and expands multiple early discoveries: verifying that vaccines can effectively activate humoral immunity after breaking through infection； Revealing the ability of RNA viruses to escape quickly under continuous mutation pressure ； Expand the understanding of the concept of "herd immunity": In the face of rapid mutant viruses, herd immunity cannot be achieved once and for all and must be dynamically maintained. It has formed strong mutual proof with the conclusions of Omicron immune escape and vaccine efficacy in a number of international studies, which strengthened the need for immunogen renewal against mutant strains.

Omicron breakthrough infection provides a unique window to observe the interaction of immune responses with viral evolution. This study from southwestern China, based on large-scale real-world data, reveals complex dynamics between antibody production, decay, cross-reactions, and mutation escape. The new crown epidemic is no longer presented in panic, but the evolution of the virus is still quietly going on. This study uses real data to reveal to us: population immunity is not a one-time construction, but a dynamic process of dancing with the virus.

Every infection, every vaccination, and the emergence of every new strain are key nodes in the remodeling of the immune barrier. Only precise immunization monitoring and rapid vaccine response can truly protect public health in the post-epidemic era. Faced with the continuous evolution of SARS-CoV-2, the construction of an immune defense line cannot be achieved by just one vaccination or a single infection, but should be a long-term, flexible and scientific process. Continuous monitoring of changes in neutralizing antibodies and timely updates of vaccine composition will become one of the core pillars of the future public health system.

"Signal Transduction and Targeted Therapy" was founded in 2016. Its latest impact factor is 52.7. It is located in the JCR Q1 area. The journal is committed to publishing high-quality research related to signal transduction and targeted therapy, covering multiple fields such as molecular biology, cell biology, pharmacology, medicinal chemistry, clinical medicine, etc., and aims to become an important platform for international academic exchanges.

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https://pubs.acs.org/doi/10.1021/acsnano.5c02492