Immune Response Dynamics in Solid Organ Transplant Recipients After Omicron Booster Vaccinations

Participants who had hybrid immunity due to previous SARS-CoV-2 infection showed higher overall neutralization against the XBB15 variant and sustained this neutralization beyond 3 months post-bivalent booster, indicating possible adaptability in booster timing depending on prior infection.

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A recent study published in Clinical Infectious Diseases has revealed the immune response dynamics in solid organ transplant recipients (SOTRs) after receiving Omicron-containing booster vaccinations. Researchers found that initial bivalent mRNA vaccine boosters (BvB1) temporarily increased neutralization against variants BA4/5 and XBB15, these responses declined significantly by 3 months post-boost. Subsequent boosters (BvB2) partially restored neutralization levels, yet some participants did not achieve adequate neutralizing inhibition against the XBB15 variant.

Among the 76 SOTRs studied, the median %ACE2 inhibition, a surrogate marker for neutralizing antibodies, increased notably post-BvB1 against BA.4/5 (from 42% to 63%) and XBB.1.5 (18% to 43%). However, these gains diminished by 3 and 6 months post-BvB1.

Correspondent on this study, Andrew H Karaba, MD, PhD, Assistant Professor of Medicine in the Division of Infectious Diseases and Associate Director of Basic/Translational Research at the Transplant Research Center at Johns Hopkins University explains the processes further,

“We used the ACE2 (Angiotensin-Converting Enzyme 2) inhibition assay from Meso Scale Discovery (MSD) which is a multiplexed, high-throughput, competitive inhibition-based ELISA (Enzyme-Linked Immunosorbent Assay). This assay allowed us to test surrogation neutralization (the ability of participant plasma to inhibit SARS-CoV-2 Spike binding to ACE2) of several variants of concern at once. We then used the statistical tests described in the methods to compare surrogate neutralization over time after vaccination.”

Following BvB2, %ACE2 inhibition against XBB15 improved from 15% pre-boost to 28% post-boost, though achieving neutralizing inhibition remained a challenge for 42% of participants.

“We determined that for XBB15, neutralization levels waned by 3 months such that they were no different than before the bivalent boost. This was restored with a second boost, but did not improve the response beyond what was seen with the first boost,” explains Karaba.

Participants received a minimum 3-dose primary monovalent vaccine series followed by bivalent mRNA vaccine boosters. Blood samples were collected at regular intervals post-boosts, and %ACE2 inhibition was assessed using MSD assays. Statistical analyses included Wilcoxon rank-sum, Fisher exact, and longitudinal modeling using R and Stata. This study was conducted between June 2022 and June 2023.

Hybrid immunity, facilitated by repeated boosters, enhanced both the peak level and duration of neutralizing antibodies against coronavirus variants. However, responses varied significantly between different variants, with notable differences observed in the efficacy against XBB.1.5 post-BvB1 and BvB2.

The study’s limitations include the observational nature and relatively small sample size, limiting the generalizability of findings. Additionally, the study focused on humoral vaccine responses and did not evaluate T-cell responses or live virus-neutralizing antibodies.

Karaba continues, “Those with hybrid immunity (evidence of previous SARS-CoV-2 infection) had higher overall neutralization of XBB15. Furthermore, those with hybrid immunity-maintained neutralization beyond 3 months post-bivalent boost. So, while overall our findings suggest that frequent (every 3-6 months) may be necessary to maintain neutralizing antibody levels in transplant patients against emerging variants, those that had a relatively recent infection may be OK to get boosters closer to the 6-month part of that range, and getting a booster within 3 months of a recent infection is likely unnecessary.”

In conclusion, this study underscores SOTRs in maintaining robust immune responses against evolving SARS-CoV-2 variants post-vaccination. Regular boosting every 6 months should sustain effective neutralization, highlighting the ongoing need for tailored vaccination strategies in this high-risk population.

References

1. Karaba A, Werbell W, Johnston T, et. al Rapid Wane and Recovery of XBB Sublineage Neutralization After Sequential Omicron-based Vaccination in Solid Organ Transplant Recipients Get access Arrow. Clinical Infectious Diseases. Published July 2, 2024. Accessed July 3, 2024. https://www.hopkinsmedicine.org/news/newsroom/news-releases/2024/07/study-suggests-regular-vaccine-boosts-may-help-people-who-are-immunocompromised-fight-covid-19-press

2. Study Suggests Regular Vaccine Boosts May Help People Who Are Immunocompromised Fight COVID-19. Newsroom. Published July 2, 2024. Accessed July 3, 2024. https://www.hopkinsmedicine.org/news/newsroom/news-releases/2024/07/study-suggests-regular-vaccine-boosts-may-help-people-who-are-immunocompromised-fight-covid-19-press