.jpg)
Researchers tested the antibodies raised by mRNA vaccination and compared them with those from natural SARS-CoV-2 infection. They found that the vaccine did not have antibodies to the virus nucleocapsid protein, but potent RBD antibodies.
Several vaccines have been approved to combat the COVID-19 pandemic. The vaccines based on the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA), for example those developed by Moderna and Pfizer, have demonstrated exceptional efficacy. There is some evidence that strong protection is afforded within two weeks of vaccination.
Researchers at the University of California, Irvine examined the immune response produced by mRNA vaccines to better understand how they relate to antibodies generated by the natural severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Their results are published on the bioRxiv * preprint server.
The authors used data from ongoing seroprevalence studies in Orange County, California. The first survey was conducted in July 2020 and the second in December 2020. Samples collected from surveys by the University of California Irvine Medical Center in May and December 2020 were also analyzed.
Samples from vaccinated individuals were collected in January, February and March 2021. They used the coronavirus antigen microarray to measure antibodies against 37 coronaviruses and influenza antigens.
.jpg?resize=560%2C320&ssl=1 "Study: Significant differences in SARS-CoV-2 antibody responses caused by natural infection and mRNA vaccination. Image Credit: MattLphotography / Shutterstock")
Antibodies differ in vaccination and natural infection
The seroprevalence in Santa Ana postal codes was 18% in July 2020 and 26% in December 2020. In the hospital, the seroprevalence was 13% in December 2020. After the vaccination started in the hospital, there was 98.7% seroprevalence against the end of March 2021, suggesting that the mRNA vaccine may elicit a strong antibody response.
There was a difference between the antibodies elicited by natural infection as compared to that of the vaccine. Since the vaccine does not contain the nucleocapsid protein, there are no antibodies against it in the antibodies induced by the vaccine. However, antibodies to nucleocapsid were seen in natural infection, suggesting that this could be a biomarker of natural infection.
Further investigation showed that vaccines elicited more antibodies against the spike protein receptor binding domain (RBD) compared to the antibodies seen in natural infection. All individuals had seasonal influenza and cold antibodies, and the levels were the same for everyone regardless of whether they had COVID-19.
Natural infection produces antibodies against the nucleocapsid and all fragments of the spike protein. The highest antibody levels were against the nucleocapsid, full-length spike protein, and the S2 subunit. Antibody levels against RBD were weak and could be a mechanism for the development of new virus variants
Vaccinated individuals showed high antibody levels against the full-length spike protein, S2 subunit, and much higher levels against the RBD and S1 subunit. These individuals also had cross-reactive antibodies between the spike protein and RBD, absent in natural infection.
The mRNA vaccine likely adopts a protein conformation that displays cross-reactive epitopes. This could be useful against emerging virus variants and suggests that the antibodies produced may still be effective against them.
mRNA vaccines elicit a strong antibody response
Natural infection produces a uniform level of antibodies to the nucleocapsid and spike proteins. Vaccinated individuals fall into two groups, those with antibodies to the nucleocapsid protein and those without. Those with nucleocapsid antibodies may have been previously infected naturally.
Longitudinal samples taken at weekly intervals from 9 individuals before and after vaccination against mRNA. Individuals differ significantly in their response to the prime. Five subjects had a low NP reactivity at baseline that did not change after vaccination. Four subjects had an increased NP reactivity at baseline, which also did not change significantly after vaccination; topic # 3 was a recovered confirmed COVID case. In this small group, a higher NP predicts a higher response after prime. These results support a guideline for getting the boost to achieve more uniform protection within a population of individuals.
Some individuals showed good antibody levels after the first dose, but most required a booster dose for robust antibody levels observed approximately 35 days after the first dose. The data also suggests that people previously infected naturally have a more robust antibody response to the vaccine.
The study results are comparable to the antibody levels seen in clinical studies with the mRNA vaccines and show rapid antibody production. High levels of antibodies to the RBD seen in vaccinated individuals indicate good protection. The RBD is the portion of the spike protein that binds on host cells to the angiotensin converting enzyme 2 (ACE2) receptor.
Antibodies from natural infection do not have high levels against the RBD. This could be because the RBD epitope may be hidden to prevent host immune recognition. The less robust and variable antibody response to natural infection suggests that immunity obtained by natural infection may not be as strong as that obtained by vaccination. “We should not assume that previously infected individuals are immune or that they cannot transmit the virus,” the authors write.
Thus, vaccination elicits a more potent antibody response, and even people who have been previously infected can benefit from the vaccine.
*Important announcement
bioRxiv publishes preliminary scientific reports that are not peer-reviewed and therefore should not be considered conclusive, serve clinical practice / health-related behavior, or be treated as established information.