COVID-19 vaccination and utility of booster dose: A community-based cross-sectional study

Vaccine. 2025 Jul 11:60:127325. doi: 10.1016/j.vaccine.2025.127325. Epub 2025 May 29.

Abstract

Background: In 2023, the WHO declared the end of the COVID-19 pandemic, cautioning that the virus will continue to mutate and may cause sporadic outbreaks. Vaccination was critical in controlling the pandemic, though concerns persist about long-term immunity and the need for booster doses. The study aimed to assess whether vaccination enhances immunity beyond natural infection and determine the ongoing need for booster doses.

Methods: This population-based cross-sectional study was conducted across ten districts in Uttar Pradesh, India, to evaluate humoral and cellular immune responses in vaccinated individuals (ChAdOx1nCoV-19 vaccine & BBV152) or those previously infected with SARS-CoV-2. Six hundred forty-three participants were assessed for cellular immunity and 7000 for humoral immunity. Anti-receptor binding domain (RBD) antibodies were measured using enzyme-linked immunoassay (ELISA), and various subsets of memory T-cells were analyzed via flow cytometry.

Results: The study revealed that vaccination significantly elevated antibody titers compared to natural infection (p < 0.001), with the most significant increase observed after the second dose (p < 0.001). While subsequent doses raised antibody levels, the increase between the second and third doses was modest. T-cell responses, particularly memory subsets such as effector memory (p = 0.009), central memory (p = 0.003), and stem cell memory (p < 0.001), showed significant enhancement after the second dose but plateaued following the third dose, suggesting further doses may not be beneficial.

Conclusion: While vaccination effectively increases antibody levels and reduces hospitalizations and severe outcomes, additional booster doses may offer limited benefits for the general population, as there appears to be a ceiling effect in both humoral and cellular immunity after the second dose. Given the potential adverse effects of COVID-19 vaccination, the decision to administer multiple booster doses to specific population groups must be based on further studies that directly address this issue, along with a thorough risk-benefit analysis.

Keywords: Antibodies; CD4 + T; CD8 + T; COVID-19; Flow cytometry; Immunity; Vaccination.

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Viral / blood
  • Antibodies, Viral / immunology
  • COVID-19 Vaccines* / administration & dosage
  • COVID-19 Vaccines* / immunology
  • COVID-19* / epidemiology
  • COVID-19* / immunology
  • COVID-19* / prevention & control
  • ChAdOx1 nCoV-19 / immunology
  • Cross-Sectional Studies
  • Female
  • Humans
  • Immunity, Cellular
  • Immunity, Humoral
  • Immunization, Secondary* / methods
  • India / epidemiology
  • Male
  • Middle Aged
  • SARS-CoV-2* / immunology
  • Vaccination
  • Young Adult

Substances

  • Antibodies, Viral
  • COVID-19 Vaccines
  • ChAdOx1 nCoV-19