The antibody response induced by mRNA vaccination differs from natural SARS-CoV-2 infection

The researchers tested the antibodies caused by the mRNA vaccination and compared them with those from the natural SARS-CoV-2 infection. They found that the vaccine had no antibodies against the virus’s nucleocapsid protein, but had potent RBD antibodies.

Several vaccines have been approved to combat the COVID-19 pandemic. Severe coronavirus 2 messenger RNA (mRNA) (SARS-CoV-2) vaccines, for example, those developed by Moderna and Pfizer, have shown 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 in 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. The samples collected from surveys at the University of California’s Irvine Medical Center in May and December 2020 were also analyzed. .

Samples of vaccinated individuals were collected in January, February, and March 2021. They used the coronavirus antigen microarray to measure antibodies against 37 coronavirus and influenza antigens.

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 hospital vaccination began , there was 98.7% seroprevalence at the end of March 2021, suggesting that the mRNA vaccine is capable of obtaining a strong antibody response.

There was a difference between the antibodies caused by the natural infection compared to those of the vaccine. Because the vaccine does not have the nucleocapsid protein, there are no antibodies against it in the vaccine-induced antibodies. However, antibodies against the nucleocapsid were observed in the natural infection, suggesting that this could be a biomarker of the natural infection.

Subsequent tests revealed that vaccines cause more antibodies against the peak protein receptor binding domain (RBD) compared to antibodies seen in natural infection. All individuals had antibodies against seasonal flu and cold and the levels were the same for all, regardless of whether they had COVID-19.

Natural infection produces antibodies against the nucleocapsid and all fragments of the ear protein. The highest levels of antibodies were against the nucleocapsid, the full-length spike protein, and the S2 subunit. Antibody levels against RBD were weak and could be a mechanism for the evolution of new virus variants.

Vaccinated individuals showed elevated levels of antibodies against the full-length ear protein, the S2 subunit, and much higher levels of the RBD and S1 subunit. These individuals also had cross-reactive antibodies between spike protein and RBD, absent in the natural infection.

The mRNA vaccine is likely to adopt a protein conformation presenting cross-reactive epitopes. This could be useful against emerging variants of viruses and suggests that the antibodies produced could still be effective against them.

MRNA vaccines elicit a strong antibody response

Natural infection produces a uniform level of antibodies against the nucleocapsid and ear protein. Vaccinated individuals are divided into two groups, those that have antibodies to the nucleocapsid protein and those that do not. Those with nucleocapsid antibodies may have been naturally infected before.

Longitudinal samples taken at weekly intervals from 9 pre- and post-mRNA vaccinated individuals. Individuals differ substantially in their response to the former. Five individuals had a basal NP reactivity that did not change after vaccination. Four individuals had elevated NP reactivity at baseline, which also did not change significantly after vaccination; item 3 was a recovered recovered COVID case. In this small group, higher basal NP predicts a higher response after the first. These results support a directive to get the impetus to achieve 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 to obtain robust levels of antibodies, which were seen about 35 days after the first dose. The data also suggest that people who have previously been naturally infected 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, which show rapid antibody production. The high levels of RBD antibodies observed in vaccinated individuals suggest good protection. RBD is the portion of the spike protein that binds to the angiotensin 2 converting enzyme (ACE2) receptor in host cells.

Natural infection antibodies do not have high levels against 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 the immunity acquired by natural infection may not be as strong as that of vaccination. “We should not assume that previously infected people are immune or unable to transmit the virus,” the authors write.

Therefore, vaccination induces a more robust antibody response and even people who have been previously infected can benefit from the vaccine.

* Important news

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