Table 2.
Studies reporting effects of pre-existing immunity on vaccine effectiveness.
| Study (first author, year) | Study title | Study type | Summary of study findings | DOI (for source verification) |
|---|---|---|---|---|
| (A) Positive effects | ||||
| Velázquez F. R., 1996 (126) | Rotavirus infection in infants as protection against subsequent infections | Cohort study | Natural rotavirus infection provides progressive protection against subsequent infection and severe disease. | 10.1056/NEJM199610033351404 |
| Rogawski. E. T., 2018 (127) | Quantifying the impact of natural immunity on rotavirus vaccine efficacy estimates | Clinical trial and simulation study | Previous natural rotavirus infection in children provides greater protection and can enhance vaccine efficacy. | 10.1093/infdis/jix668 |
| Levine M. M., 1981 (128); Pasetti M. F., 2012 (129) | Duration of infection-derived immunity to cholera; Insights from natural infection-derived immunity to cholera instruct vaccine efforts | Human challenge study; commentary article | Infection-derived immunity to cholera is long-lasting; this formed the basis of designing oral live vaccines to induce natural immunity. | 10.1093/infdis/143.6.818;10.1128/CVI.00543-12 |
| Kim J. H., 2016 (130) | Prior infection with influenza virus but not vaccination leaves a long-term immunological imprint that intensifies the protective efficacy of antigenically drifted vaccine strains | Experimental immunology study on a mouse model | Prior influenza infection, more than prior vaccination in some contexts, can improve the magnitude and breadth of responses to subsequent variant vaccines. | 10.1016/j.vaccine.2015.11.077 |
| Spinardi J. R., 2023 (131) | Hybrid immunity to SARS-CoV-2 from infection and vaccination—evidence synthesis and implications for new COVID-19 vaccines | Narrative review | Hybrid immunity derived from a combination of previous infection and vaccination confers stronger and broader protection against reinfection and severe disease than vaccination or infection alone. | 10.3390/biomedicines11020370 |
| Andrade A. G., 2023 (132) | Natural and hybrid immunity: a comparative study of T cell response against SARS-CoV-2 | Case–control comparative immunological study | Vaccines complement pre-existing immunity from natural infection by orchestrating a more proficient antiviral immune response with an immuno-regulatory capacity. | 10.1016/j.clicom.2025.07.001 |
| Bobrovitz N., 2023 (121) | Protective effectiveness of previous SARS-CoV-2 infection and hybrid immunity against the omicron variant and severe disease | Systematic review and meta-regression | Individuals with hybrid immunity from both natural infection and vaccination had the highest magnitude and durability of protection. | 10.1016/S1473-3099(22)00801-5 |
| (B) Negative effects | ||||
| Ali M., 2011 (112) | Natural cholera infection–derived immunity in an endemic setting | Cohort analysis | Efficacy of vaccines against cholera is lower in endemic settings due to the presence of substantial long-lasting protection from natural infection. | 10.1093/infdis/jir416 |
| Bradt V., 2019 (133) | Pre-existing yellow fever immunity impairs and modulates the antibody response to tick-borne encephalitis vaccination | Clinical case–control study | Pre-existing immunity from yellow fever vaccinations impaired neutralizing antibody activity against tick-borne encephalitis virus—described as original antigenic sin as both are flaviviruses. | 10.1038/s41541-019-0133-5 |
| Santos-Peral A., 2024 (134) | Prior flavivirus immunity skews the yellow fever vaccine response to cross-reactive antibodies with potential to enhance dengue virus infection | Clinical cohort | Prior flavivirus immunity derived from vaccination against tick born encephalitis virus skews immune responses against subsequent yellow fever vaccination towards more cross-reactive antibodies with a lower neutralizing potential and can enhance dengue virus infection. | 10.1038/s41467-024-45806-x |
| Zarnitsyna V. I., 2016 (135) | Multi-epitope models explain how pre-existing antibodies affect the generation of broadly protective responses to influenza | Mathematical modelling | Pre-existing antibodies from previous infection and vaccinations mask antigens which prevents effective boosting of protective responses. | 10.1371/journal.ppat.1005692 |
| Monto A. S., 2017 (136) | The doctrine of original antigenic sin: separating good from evil | Narrative review | Highlights studies showing that secondary exposures to different strains of influenza and to influenza vaccinations result in an attenuated immune response. | 10.1093/infdis/jix173 |
| Roy S., 2020 (137) | Impact of pre-existing immunity to influenza on live-attenuated influenza vaccine (LAIV) immunogenicity | Narrative review on pre-clinical and clinical studies | Pre-existing antibodies limit replication of live attenuated influenza vaccines and subsequent induction of T cells; hence reducing vaccine effectiveness. | 10.3390/vaccines8040683 |
| Xie Y., 2023 (138) | Immune interference in effectiveness of influenza and COVID-19 vaccination | Narrative review | Reviews evidence on the role of prior immunity from repeated exposure to influenza and COVID-19 either via natural infection or multiple vaccinations on the effectiveness of subsequent vaccinations. | 10.3389/fimmu.2023.1167214 |
| Wrynla X. H., 2025 (110) | Immune imprinting and vaccine interval determine antibody responses to monovalent XBB.1.5 COVID-19 vaccination | Case–control clinical immunogenicity | Pre-existing immunity affects humoral immunity elicited by an updated variant vaccine as antibodies against the original virus were boosted over variant-specific antibodies from the updated vaccine. | 10.1038/s43856-025-00898-4 |
| Fausther-Bovendo H., 2014 (139) | Pre-existing immunity against Ad vectors: humoral, cellular, and innate response, what’s important? | Narrative review | Prior immunity against vaccine vectors can neutralize and clear the vector which subsequently reduces overall vaccine immunogenicity and reduces vaccine efficacy. | 10.4161/hv.29594 |