Healthy, cancer, and immunosuppressed patients all benefit from COVID boosters

In a recent study posted to the medRxiv* pre-print server, researchers developed a mechanistic mathematical model to predict the course of vaccine-induced immunity in healthy and immunosuppressed patients for the long term, exceeding the time frames for which clinical data is currently available.

Study: Mechanistic model for booster doses effectiveness in healthy, cancer and immunosuppressed patients infected with SARS-CoV-2. Image Credit: eamesBot

Background

Previous studies have established that booster doses are required to maintain adequate immune protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in immunocompromised patients. However, persistence over time and efficacy against novel or yet to emerge SARS-CoV-2 variants is uncertain. More importantly, there is no framework to predict optimal vaccination strategies for high-risk patient populations suffering from rapid waning immunity following vaccination.

About the study

In the present study, researchers investigated the effect of homologous vaccination, including a booster dose, on immunity and severity of clinical course following SARS-CoV-2 infection with ancestral and variant strains. The model parameters included the affinity of cells for vaccine particles and their uptake rate, the deoxyribonucleic acid (DNA) to messenger ribonucleic acid (mRNA) transcription rate, the rate of production and degeneration of viral antigens, and the degradation rates of the vaccine.

They fitted model predictions to clinical data of average values of antibodies directed against the SARS-CoV-2 spike (S) protein in healthy individuals who received two doses of the mRNA-based BNT-162b2a or mRNA-1273 vaccines or the Ad26.COV2.S viral vector vaccine and computed the baseline values of all model parameters. Further, the team repeated simulations using 100 different values for each parameter within an order of magnitude around the baseline values to identify the best-fit parameter values.

Furthermore, they compared model predictions with additional data from seven independent clinical studies on booster doses that covered vaccinated healthy participants and cancer patients receiving chemotherapy or programmed death-1 (PD-1) immune checkpoint blockers. Moreover, they simulated the effects of vaccination for 100 weeks, including a third dose for the mRNA vaccines and a second dose of the vector vaccine. Further, the researchers examined the effects of vaccination on the levels of immune cells that influence the severity of viral infection. The team also investigated the impact of new SARS-CoV-2 variants on immunosuppressed patients who had received a booster dose. The baseline values of infection-related with the Delta variant served as control.

Additionally, they modulated several parameters in the model to mimic SARS-CoV-2 variants with different affinity for angiotensin-converting enzyme 2 (ACE2) and antigenicity. Likewise, those that internalized and replicated differently in host cells, released virions at a different rate from infected cells and also differed in their clearance rate (by antibodies). Finally, they accounted for variations in each of these parameters separately, assuming exposure to the virus occurred six months after the booster dose.

Study findings                              

The study model accurately predicted antibody dynamics directly linked to immune protection from SARS-CoV-2 infection. The model predicted a substantial reduction in the antibody within six months following vaccination with all types of vaccines. However, it also predicted a rapid increase in antibody levels following a booster dose. While the antibody levels following a booster dose remained above 10,000 U/ml for the healthy mRNA vaccinees and 1,000 U/ml for the healthy vector vaccinees for the entire simulated period, they reached lower values for cancer and immunosuppressed patients with or without cancer.

Within six months from the second mRNA vaccination, B cells, cluster of differentiation (CD)4⁺, CD8⁺ T cells, and antigen-presenting cells (APCs) declined up to 50%, the same as the observed decrease in antibody levels. In the Ad26.COV2.S  vaccine recipients, this decrease in the six months was less pronounced, but the attained peak levels were also significantly lower compared to the mRNA vaccine recipients. However, following a booster dose, all anti-SARS-CoV-2 immune cells increased except for immunosuppressed individuals who exhibited less than 50% increase in all immune cells. The 100-week simulation predicted a double the number of all immune cells against SARS-CoV-2 in healthy individuals and cancer patients receiving PD-L1/PD-1 inhibition therapy.

Conclusions

The study confirmed the advantages of mRNA vaccines over vector vaccines by simulating the decreased immune responses in healthy and immunosuppressed patients six months after vaccination. The study also demonstrated that a booster dose of mRNA vaccines induced adequate protection for more than a year in healthy patients. However, the immunosuppressed patients, including those receiving chemotherapy or B cell depletion treatment, showed a waning booster effect, thus, requiring boosters frequently. To conclude, the study results could help inform the time for booster vaccinations for individuals with different phenotypes and comorbidities and against novel SARS-CoV-2 variants.

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.