.jpg "Antibody response induced by mRNA vaccination differs from natural SARS-CoV-2 infection")
Researchers tested the antibodies of mRNA vaccination and compared it to that of natural SARS-CoV-2 infection. They found that the vaccine does not have antibodies to the nucleocapsid protein, but that it has powerful RBD antibodies.
Several vaccines have been approved to combat the COVID-19 pandemic. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA) -based vaccines, for example those developed by Moderna and Pfizer, have shown exceptional efficacy. Evidence indicates strong protection within two weeks after vaccination.
Researchers from the University of California, Irvine, examined the immune response produced by mRNA vaccines to better understand how it compares to antibodies generated by natural severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Their results are based on the bioRxiv * preprint server.
The authors used the data from ongoing seroprevalence studies in Orange County, California. The first survey was conducted in July 2020, and the second was conducted in December 2020. Samples also collected by the University of California Irvine Medical Center in May and December 2020 were analyzed.
Samples of vaccinated individuals were collected in the months of 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 responses to the antibodies of SARS-CoV-2 caused by natural infection and mRNA vaccination. Image Credit: MattLphotography / Shutterstock")
Antibodies that differ in vaccination and natural infection
The seroprevalence in the Santa Ana zip 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, indicating that the mRNA vaccine is capable of eliciting a strong antibody response.
There was a difference between the antibodies produced by natural infection compared to the vaccine. Since the vaccine does not contain the nucleocapsid protein, there are no antibodies against it in the vaccine-induced antibodies. However, antibodies to nucleocapsid have been seen in a natural infection, suggesting that it may be a biomarker for natural infection.
Further tests showed that vaccines elicit more antibodies against the protein receptor-binding domain (RBD) compared to the antibodies seen in natural infections. All individuals had antibodies to seasonal flu and colds, 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 vein protein. The highest antibody levels were against the nucleocapsid, full-length ear protein and the S2 subunit. Antibody levels against RBD were weak and may be a mechanism for developing new virus variants
Vaccines have high antibody levels versus the full-length peak protein, S2 subunit, and much higher levels for the RBD and S1 subunit. These individuals also have cross-reactive antibodies between the vein protein and RBD, absent in natural infection.
The mRNA vaccine probably accepts a protein conformation that provides cross-reactive epitopes. It can be useful against emerging virus variants and suggests that the antibodies produced may still be effective against it.
mRNA vaccines elicit a strong antibody response
Natural infection produces a uniform level of antibodies against the nucleocapsid and vein protein. Vaccinated individuals fall into two groups, those with antibodies to the nucleocapsid protein and those without. Those with nucleocapsid antibodies may have been naturally infected in the past.
Lung samples are taken weekly between 9 individuals before and after mRNA vaccination. Individuals differ significantly in their response to the first. Five individuals had a low baseline reactivity that did not change after vaccination. Four individuals had an increased NP reactivity at baseline that also did not change significantly after vaccination; topic 3 was a confirmed COVID case. In this small group, NP a higher baseline predicts a higher response after the first time. These results support a mandate to get 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, which were seen approximately 35 days after the first dose. The data also suggest that people who have been naturally infected in the past have a more robust antibody response to the vaccine.
The results of the study are similar to the antibody surveys seen in clinical trials of the mRNA vaccines, which show a rapid production of antibodies. High levels of RBD antibodies found in vaccines indicate good protection. The RBD is the portion of the vein protein that binds to the angiotensin-converting enzyme 2 (ACE2) receptor on host cells.
Antibodies of natural infection do not have high levels against RBD. This may be because the RBD epitope may be hidden to prevent immune recognition from the host. The less robust and variable antibody response to natural infection suggests that immunity acquired through natural infection may not be as strong as against vaccination. “We must not assume that previously infected individuals are immune or that they cannot transmit the virus,” the authors write.
Vaccination therefore elicits a more robust antibody response, and even previously infected people can benefit from the vaccine.
* Important notice
bioRxiv publishes preliminary scientific reports that are not judged by peers, and therefore should not be considered conclusive, should guide clinical practice / health-related behavior, or should be treated as established information.