Humoral immunity following heterologous and homologous COVID-19 vaccination regimens

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causal agent of the coronavirus disease-19 (COVID-19) pandemic. Since its emergence in 2019, it has claimed about five million lives and ravaged the global economy. It has been reported that the novel SARS-CoV-2 can trigger autoimmunity. Therefore, it is important to study whether anti-SARS-CoV2 vaccines evoke the formation of autoantibodies and subsequent autoimmunity.

Study: Anti-SARS-CoV-2 vaccination does not induce the formation of autoantibodies but provides humoral immunity following heterologous and homologous vaccination regimens: Results from a clinical and prospective study within professionals of a German University Hospital. Image Credit: ezps/ Shutterstock

In a new study, published on the medRxiv* preprint server, researchers sought to analyze immune responses after homologous vaccinations or after heterologous Vector/mRNA vaccinations, with respect to anti-COVID-19 immune responses and the development of autoantibodies.

Background

In half of the COVID-19 cases, the infection shows an inapparent disease course, thereby favoring the undetected spread of the virus. In severe cases, COVID-19 affects the skin, the kidneys, the nervous system, and the hematological system, besides the lungs. Such infections often show hyperactivation of neutrophils and excessive production of pro-inflammatory cytokines (similar to patients suffering from autoimmune diseases). Therefore, the immune reaction in response to SARS-CoV-2 infections is akin to autoimmune diseases.

Scientists have reported that COVID-19 patients carrying anti-nuclear antibodies (ANAs), anti-phospholipid antibodies, or anti-SS-A/Ro show more severe outcomes than patients lacking these autoantibodies. In asymptomatic patients, an age-dependent tendency towards the development of autoantibodies was detected.

By the end of 2020, three COVID-19 vaccines were approved in Germany – BioNTech´s Comirnaty and Moderna´s Spikevax (using mRNA techniques) and AstraZeneca’s Vaxzevria (using a non-replicating chimpanzee adenovirus). All three vaccines appeared safe and showed significant efficacy in clinical trials. However, no systematic clinical study assessing whether COVID-19 vaccination also triggers the production of autoantibodies has been published yet. To this end, in the present study, researchers analyzed anti-SARS-CoV2 and autoantibody responses before and after applying heterologous and homologous vaccination protocols against COVID-19.

A new study

The participants are from the CoVac study that started in April 2021 and is an ongoing observational study surveying the induction of autoimmunity upon COVID-19 vaccination. Participants were from the University Hospital Magdeburg and the Medical Faculty of the Otto-von-Guericke-University Magdeburg. They received prime injections with Spikevax, Vaxzevria, or Comirnaty. Homologous booster doses, by Spikevax and Comirnaty, were administered after 28 and 41 days, respectively. Participants who received a homologous vaccination with either Spikevax or Comirnaty were combined in the mRNA/mRNA group. The sample comprised of 36% males with a mean age of 36 years for the mRNA/mRNA group, 47 years for the Vector/Vector group, and 38 years for the Vector/mRNA group.

Main findings

The research revealed a remarkable difference in SARS-CoV2 specific IgG antibodies when comparing homologous vaccination with mRNA or vector-based vaccines. The number of antibodies produced in the Vector/Vector group was 10% of that in the mRNA group. Additionally, virus neutralization appeared significantly less effective in the former group. Scientists opined that serum IgG and/or neutralizing antibodies might not be the best measure for protection. Cellular immunity could contribute to the protection after vaccination and, hence, needs to be considered a correlate of protection.

The T cell-mediated immunity was also observed to be weaker upon Vaxzevria vaccination compared to mRNA vaccination. However, it is currently unknown how strong T cell reactions need to be to protect against SARS-CoV-2. To address this issue, more research analyzing humoral and cellular immunity is needed. If it is proved that humoral immunity after homologous Vaxzevria immunization is weaker, the third vaccination with an mRNA vaccine might be required.

In the current study, a heterologous vaccination strategy (Vaxzevria followed by an mRNA boost) was as effective, in the induction of anti-Sp1-IgG antibodies, as a homologous mRNA vaccination. However, the pan-antibody response (also including IgA and IgM) was much stronger upon heterologous vaccination. The observations presented in this paper, especially with respect to the production of SARS-CoV2-specific IgA, might be of special interest.

In the context of COVID-19 infections, various reports described the appearance of autoantibodies and their correlation with more severe diseases. This study is the first that systematically addresses this issue. Scientists did not detect induction of autoantibodies upon booster vaccination in all three study groups. In females, upon heterologous vaccination, β2-Glycoprotein autoantibodies slightly increased, but they remained below the cutoff.

Conclusion

Researchers analyzed immune responses after homologous (mRNA or vector virus-based) or heterologous (Vector/mRNA) vaccinations with respect to anti-COVID-19 immune responses and the development of autoantibodies. The results indicated that the appearance of autoantibodies is a transient event that occasionally accompanies the vaccination but does not have clinical relevance. This result, however, does not hold for a vaccination with new vaccines or repetitive vaccinations with the same vaccines. A couple of limitations of the study relate to the small sample size and short observation period. Future analyses of greater cohorts are necessary and such studies should also include a healthy control group to improve the predictive power.

*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

Dr. Priyom Bose

Priyom holds a Ph.D. in Plant Biology and Biotechnology from the University of Madras, India. She is an active researcher and an experienced science writer. Priyom has also co-authored several original research articles that have been published in reputed peer-reviewed journals. She is also an avid reader and an amateur photographer.