Polyethylene glycol-specific antibody responses induced by mRNA-1273 COVID-19 vaccine

In a recent study posted to the medRxiv* preprint server, researchers determined the impact of coronavirus disease 2019 (COVID-19) vaccines on polyethylene glycol (PEG)-specific antibody responses.

Background

Various studies have reported different adverse reactions after the administration of the messenger ribonucleic acid (mRNA)-1273 (Moderna) and BNT162b2 (Pfizer) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines. However, the cause of these reactions to these mRNA-based formulations is not known.

About the study

In the present study, the researchers evaluated serum antibody (Abs) reactions to mRNA-based vaccines as compared to heterologous/homologous mRNA vaccine formulations. They also assessed the different patterns and target components of Ab reactions induced by mRNA-1273 or BNT162b2 vaccination.

The study investigated the vaccine-induced reactions to components of the vaccine formulation by collecting samples from individuals who were vaccinated with either the BNT162b2 or mRNA-1273 vaccines. The team obtained these samples from participants at baseline, 18.9 days after primary vaccination, and 19.3 days after the booster vaccination was administered. The level of Ab induction post-vaccine administration was measured via enzyme-linked immunosorbent assay (ELISA) by comparing immunoglobulin (IgG) titers to that of the SARS-CoV-2 recombinant spike protein.  

The vaccine component targeted by the mRNA-1273-induced Abs was ascertained by using ELISA plates coated with lipid nanoparticles (LNPs) bound to a SARS-CoV-2 unrelated, irrelevant mRNA. Furthermore, the team examined if the Ab induced by vaccination was reacting to PEG from the vaccine formulations. This was achieved by evaluating the levels of sera from mRNA-1273 and BNT162b2 vaccinees which were bound to PEGylated bovine serum albumin (PEG-BSA).

Moreover, the team conducted correlation analyses on the area under the curve (AUC) values obtained from the ELISAs performed. The team also assessed if the vaccines induced other anti-PEG Abs by evaluating the reactivity of IgM and IgE Abs.

Moreover, samples from individuals reporting vaccine-associated delayed onset reactions including a severe allergic reaction or injection site rashes were assessed.         

Results

The study results showed that a total of 60 longitudinal samples were collected from 10 mRNA-1273 and 10 BNT162b2 vaccinees at baseline, after primary mRNA vaccination, and after the booster vaccination. The team observed a prime-boost-dependent induction in the levels of anti-SARS-CoV-2 spike Abs after vaccination. These Ab levels ranged between 10³ AUC units after prime and 10⁴ AUC units after booster mRNA vaccination.

The team also found that the serological samples collected after mRNA-1273 vaccination had increased Ab reactivity against both mRNA-1273 and BNT162b2 vaccine formulations. Moreover, higher reactivity was observed post-booster vaccination than after prime vaccination. However, increased reactivity was not found against either of the mRNA formulations in individuals vaccinated with the BNT162b2 vaccine. Overall, only mRNA-1273 vaccination elicited Ab against one component or more of the vaccine formulations.   

Furthermore, higher levels of reactivity were found in mRNA-1273 vaccinees against the irrelevant mRNA-LNPs, as compared to those in BNT162b2 vaccinees. This suggested that the reactivity did not depend on the mRNA sequence of the vaccine formulation.

Similarly, individuals who had received the mRNA-1273 vaccine showed a significant increase in the Ab titers against PEG-BSA. Altogether, the Ab reaction might be against PEG, which is present in both the vaccine formulations.    

The team remarked that the Abs elicited after mRNA-1273 vaccine administration against the mRNA-1273 and BNT162b2 vaccine formulations correlated with PEG present in the formulations. Furthermore, a significant correlation was found between the irrelevant mRNA-LNPs and the PEGylated-BSA AUC values. The independent correlation of PEGylated-BSA AUC values with the mRNA-1273 or the BNT162b2 formulations, or with the levels of irrelevant mRNA-LNPs was found to be the lowest at baseline, higher after prime, and the highest after booster vaccination. 

Notably, a PEG-specific IgM was detected at low levels in individuals vaccinated with mRNA-1273, while no IgM Abs were found in the BNT-162b2 vaccinees. Also, insignificant amounts of PEG-specific IgE were observed in individuals vaccinated with either of the mRNA vaccines. The researchers also observed residual reactivity in participants vaccinated by either of the two mRNA vaccines. Overall, this suggested that mRNA-1273 vaccination resulted in the robust induction of IgG and IgM-specific Abs against PEG.

The team did not detect any substantial correlation between PEG-titers at baseline and Ab induction post-mRNA-1273 or BNT162b2 vaccination. Notably, higher amounts of anti-PEG Abs were observed in the mRNA-1273 vaccinees as compared to the BNT162b2 vaccinees.   

To summarize, the study findings showed that mRNA-1273 vaccination led to robust induction of PEG Abs. The researchers believe that the clinical importance of the induction of PEG-reactive Abs post-mRNA-1273 vaccination and the possible reaction of these Abs with other PEGylated drugs needs further research.

*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.

Written by

Bhavana Kunkalikar

Bhavana Kunkalikar is a medical writer based in Goa, India. Her academic background is in Pharmaceutical sciences and she holds a Bachelor's degree in Pharmacy. Her educational background allowed her to foster an interest in anatomical and physiological sciences. Her college project work based on ‘The manifestations and causes of sickle cell anemia’ formed the stepping stone to a life-long fascination with human pathophysiology.