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The researchers tested the antibodies released from the mRNA vaccination and compared them with those from the natural SARS-CoV-2 infection. They found that the vaccine did not have antibodies to the virus’s nucleocapsid protein, but had strong RBD antibodies.
Several vaccines have been approved to combat the COVID-19 pandemic. Coronavirus 2 messenger RNA (mRNA) (SARS-CoV-2) vaccines with severe acute respiratory syndrome, for example, those developed by Moderna and Pfizer, have demonstrated exceptional efficacy. Evidence suggests strong protection within two weeks of vaccination.
Researchers at the University of California, Irvine, investigated the immune response produced by mRNA vaccines to better understand how they compare to antibodies generated by severe natural acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Their results are published on bioRxiv * prepress server.
The authors used 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 collected from surveys conducted 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: Substantial differences in responses to SARS-CoV-2 antibodies caused by natural infection and mRNA vaccination. Image credit: MattLphotography / Shutterstock")
Different antibodies in vaccination and natural infection
Seroprevalence in Santa Ana zip codes was 18% in July 2020 and 26% in December 2020. At the hospital, seroprevalence was 13% in December 2020. After vaccination began at the hospital, there was 98.7% seroprevalence until end of March 2021, suggesting that the mRNA vaccine may generate a strong response to antibodies.
There was a difference between the antibodies triggered by the natural infection compared to those in the vaccine. Because the vaccine does not have a nucleocapsid protein, there are no antibodies against it in vaccine-induced antibodies. However, antibodies to the nucleocapsid have been observed in natural infection, suggesting that this may be a biomarker for natural infection.
Subsequent tests have shown that vaccines obtain more antibodies against the peak protein receptor binding domain (RBD) compared to antibodies seen in natural infection. All individuals had antibodies against seasonal influenza, and colds and levels were the same for all, regardless of whether they had COVID-19.
The natural infection produces antibodies against the nucleocapsid and all fragments of the spike protein. The highest levels of antibodies were against nucleocapids, full-length peak protein, and the S2 subunit. Antibody levels against RBD have been low and could be a mechanism for the evolution of new virus variants.
Vaccinated individuals had high levels of antibodies against the full-length protein, the S2 subunit, and much higher levels than the RBD and S1 subunits. These individuals also had cross-reactive antibodies between the spike protein and RBD, absent in the natural infection.
The mRNA vaccine probably adopts a protein conformation with cross-reactive epitopes. This could be useful against emerging virus variants and suggests that the antibodies produced could still be effective against them.
MRNA vaccines generate a strong response to antibodies
The natural infection produces a uniform level of antibodies against the nucleocapsid and spike protein. Vaccinated individuals are divided into two groups, those with antibodies against the nucleocapsid protein and those without. Those with nucleocapsid antibodies could have been naturally infected before.
Longitudinal samples taken at weekly intervals from 9 pre- and post-mRNA vaccination individuals. The individual differs substantially in his response to the prime. Five individuals had a low reactivity of the initial NP, which did not change after vaccination. Four individuals had increased NP reactivity at baseline, which also did not change significantly after vaccination; subject no. 3 was a confirmed COVID case recovered. In this small group, higher baseline NP predicts a higher response after premiums. These results support a directive to gain the impetus for more uniform protection within a population of individuals.
Some individuals showed good levels of antibodies after the first dose, but most required a booster dose for robust levels of antibodies, which were observed about 35 days after the first dose. The data also suggest that people who have been naturally infected before have a more robust antibody response to the vaccine.
The results of the study are similar to the levels of antibodies observed in clinical trials of mRNA vaccines, showing rapid antibody production. The high levels of antibodies against RBD observed in vaccinated individuals suggest good protection. RBD is the portion of the protein that binds to the angiotensin 2 converting enzyme (ACE2) receptor on host cells.
Antibodies from natural infection do not have high levels against RBD. This may be because the RBD epitope may be hidden to prevent recognition of host immunity. The less robust and variable response of antibodies to natural infection suggests that the immunity acquired by natural infection may not be as strong as that from vaccination. “We should not assume that previously infected people are immune or unable to transmit the virus,” the authors write.
Thus, vaccination induces a more robust antibody response and even people who have been previously infected can benefit from the vaccine.
*Important Note
bioRxiv publishes preliminary scientific reports that are not evaluated by colleagues and therefore should not be considered conclusive, guide clinical practice / health-related behavior or treated as established information.