Introduction, Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne viral disease with a high fatality rate, estimated between 10 % and 30 %. BioMed Central+2Spandidos Publications+2 Despite intensive research, no licensed vaccines or proven therapies are available yet. Spandidos Publications+2Frontiers+2 One fundamental question is: Does humoral (antibody-mediated) immunity persist long term in those who recover?
Recent studies shed light on how neutralizing antibodies and memory B cells behave over time in recovered patients. Understanding this is crucial for guiding vaccine development, evaluating the efficacy of convalescent plasma therapy, and assessing the risk of reinfection.
What Is Humoral Immunity and Its Role in SFTS
Humoral immunity refers to the part of the adaptive immune system mediated by B cells and the antibodies (immunoglobulins) they produce. After a viral infection, some B cells differentiate into plasma cells, continuously secreting antibodies; others become memory B cells, which can rapidly respond to repeat exposures.
In the context of SFTS, humoral immunity is especially important because:
- Neutralizing antibodies can block viral entry into host cells, reducing or preventing further infection.
- Memory B cells allow a faster and more robust response in case of reexposure.
- Persistence of humoral immunity is a key factor for the durability of protection, whether from natural infection or vaccination.
However, SFTS — caused by the SFTS virus (also called Dabie bandavirus) — can disrupt immune function, impair B cell differentiation, or interfere with antigen presentation. Spandidos Publications+3Frontiers+3Nature+3 Viral proteins like NSs are known to antagonize innate immunity and interfere with immune signaling pathways. Frontiers+1
Evidence for Sustained Humoral Immunity After Recovery
A groundbreaking study published in Tropical Medicine and Health assessed long-term humoral immunity in survivors of SFTS. BioMed Central Key findings include:
- Detection of SFTSV Gn-specific IgG: All recovered patients had antibodies targeting the viral glycoprotein Gn, assessed by ELISA and biolayer interferometry (BLI). BioMed Central
- Neutralizing activity persists: Plasma samples from all participants retained neutralizing capacity against SFTSV; the potency (IC₅₀ values) correlated well with ELISA and BLI signals. BioMed Central
- Memory B cells detectable years later: In 12 out of 16 survivors (including those up to 6.7 years post-infection), memory B cells specific to SFTSV Gn were detected via flow cytometry. BioMed Central
These observations strongly suggest that after recovery from severe SFTS, many individuals maintain both neutralizing antibodies and memory B cells for extended periods.
Other studies support long-term antibody persistence in SFTS:
- Li et al. demonstrated the dynamics of neutralizing antibodies over several years. ScienceDirect+3BioMed Central+3Frontiers+3
- Earlier work has found SFTSV-specific IgG even 4 years after hospitalization. BioMed Central+3BioMed Central+3Frontiers+3
Thus, the weight of evidence suggests humoral immunity in many recovered individuals can last for years, though magnitude may wane with time.
Biological Basis and Challenges
How Long-Lived Plasma Cells and Memory B Cells Function
Long-lived plasma cells — residing in the bone marrow or other niches — continuously secrete antibodies even in the absence of circulating antigen. Memory B cells remain in a resting state but are ready to reactivate upon reexposure. These two arms collaborate to maintain durable humoral immunity.
Factors That Threaten Persistence
Some viral infections or immune pathologies can erode memory B cell or plasma cell pools. In SFTS, challenges include:
- Immune evasion by the virus: SFTSV can dampen interferon signaling and impair antigen-presenting cell function, indirectly compromising B cell responses. Frontiers+2Frontiers+2
- Loss or exhaustion of helper T cell function: Poor T follicular helper (Tfh) responses can hinder B cell maturation and class switching. Frontiers+1
- Declining antibody titers over time: While memory might remain, antibody levels often decline naturally, sometimes below detection thresholds.
Thus, although many survivors show durable immunity, variability exists across individuals.
Implications & Applications
Vaccine Development
The demonstration that SFTSV-specific humoral immunity can be sustained strengthens the rationale for vaccines aiming to elicit similar responses. A vaccine that successfully drives formation of long-lived plasma cells and memory B cells could confer durable protection.
Convalescent Plasma Therapy
Because survivors retain neutralizing antibodies years later, their plasma may be a source of passive immunity in acute cases. Clinical application should, however, consider antibody titers, donor screening, and timing.
Risk of Reinfection
Persistent humoral immunity likely reduces the risk or severity of reinfection. Indeed, at least one documented case of re-infection was milder than initial disease, possibly owing to residual immunity. Frontiers+1
Nevertheless, continuous monitoring of antibody levels and memory B cell frequencies in recovered cohorts is important to identify waning immunity and the need for booster vaccination strategies.
Limitations and Future Directions
- Sample sizes in long-term studies remain modest (e.g. 16 survivors in the primary study). BioMed Central
- The quality (breadth, affinity) of antibodies over time remains underexplored.
- Cell-mediated immunity (T cells) also plays a role but was less emphasized in recent humoral studies.
- Geographic, genetic, and viral strain variation might influence the durability of response.
- More longitudinal cohorts from diverse regions, with frequent sampling, are needed.
Conclusion
The accumulating evidence supports the notion that many survivors of severe fever with thrombocytopenia syndrome retain functional humoral immunity—both neutralizing antibodies and memory B cells—for years after recovery. This insight holds promise for vaccine design, passive immunotherapy, and long-term protection strategies. Still, variability among individuals and potential decline over time call for further surveillance and research.
