Study: Heterologous ChAdOx1 nCoV-19 and BNT162b2 prime-boost vaccination elicits potent neutralizing antibody responses and T cell reactivity. Image Credit: LookerStudio / Shutterstock

Heterologous AstraZeneca and Pfizer vaccines induce strong immune response and T cell reactivity against multiple SARS-CoV-2 variants

The first person to receive a coronavirus disease 2019 (COVID-19) vaccine outside a clinical trial did so within 250 days of the first case of COVID-19 being reported to the World Health Organization (WHO) in late 2019. Mass vaccination efforts are now a key strategy for controlling the pandemic. Several vaccines have been approved, including the mRNA-based BNT162b2 (Comirnaty, BioNTech/Pfizer) and the adenovirus-based ChAdOx1 nCoV-19 (Vaxzevria, AstraZeneca).

Study: Heterologous ChAdOx1 nCoV-19 and BNT162b2 prime-boost vaccination elicits potent neutralizing antibody responses and T cell reactivity. Image Credit: LookerStudio / Shutterstock

Both these vaccines induce humoral and cellular immune responses and showed high efficacy in clinical trials and significant protection from COVID-19 in the real world. However, the occurrence of rare clotting events as an adverse reaction to the ChAdOx1 nCoV-19 vaccine due to the generation of auto-platelet factor 4 antibodies led to a halt in administering second doses of the vaccine in many countries. As a result of this, many public health agencies recommend the second dose or boost vaccination to be carried out using an mRNA vaccine in a heterologous regimen for these individuals.

Analyzing immune response and T cell reactivity after heterologous ChAdOx1 nCoV-19 and BNT162b2 vaccination in a German cohort

Although heterologous prime-boost vector- and mRNA-based COVID-19 vaccines have already been administered in some people, the immunological responses to these vaccines and their level of protection are not fully understood.

Researchers from Germany recently analyzed a cohort of 26 individuals in the age range of 25 to 46 (median 30.5) years who had received a ChAdOx1 nCoV-19 prime vaccine followed by a BNT162b2 boost vaccine after a 56-day interval due to changing vaccine recommendations in Germany. There were 16 females and 10 males in the cohort, and they were assessed for immune responses, reactogenicity, and T cell reactivity. This study is published on the medRxiv* preprint server.

Results show significant increase in strong neutralization antibody titers over time

The results show that self-reported adverse reactions after ChAdOx1 nCoV-19 prime agree with previously reported symptoms and were less severe after the BNT162b2 boost vaccine. There was a significant increase in antibody titers over time which led to strong neutralization titers 2 weeks after the boost vaccine.

Neutralizing activity against the B.1.1.7 strain in individuals receiving heterologous vaccination was 3.9-fold greater than that in individuals receiving homologous BNT162b2 vaccination. Neutralizing activity was 2-fold reduced for the B.1.351 variant of concern and was similar for the B.1.617 variant. Moreover, CD4+ and CD8+ T 44 cells had reactivity to SARS-CoV-2 spike peptide stimulus 2 weeks after the prime-boost vaccination. This shows that T cell responses after heterologous vaccination are as effective as the responses after heterologous vaccination.

Findings show heterologous vaccination is effective against multiple SARS-CoV-2 variants of concern

To summarize, the heterologous ChAdOx1 nCoV-19 / BNT162b2 prime-boost vaccination regimen did not cause serious adverse events and elicited a potent humoral immune response and T cell reactivity. The B.1.1.7, B.1.351, and B.1.617 variants of concern were all potently neutralized by the sera of all participants in the study cohort. These findings suggest that a heterologous prime-boost vaccination regimen is at least as immunogenic and efficacious as homologous vaccination regimens.

According to the authors, these observations are in line with previous results and confirms that heterologous vaccination regimen was safe and effective in participants of median age 30 years. This finding offers flexibility for future vaccination strategies and may help maintain vaccination rates during shortages.

It is still unclear if heterologous vaccination regimens are superior to homologous regimens and if they should be used as a strategy to induce particularly strong immune responses in highly exposed individuals. Similarly, it remains to be seen if other vector- or mRNA-based vaccine combinations will be similarly effective in heterologous combination vaccines and future studies need to address this.

The researchers conclude:

Our immunological data suggest that a heterologous vector-based/mRNA prime-boost schedule is highly effective in preventing COVID-19, as neutralizing antibody levels correlate with immune protection from symptomatic SARS-CoV-2 infection and CD8+ T cell responses have been associated with a mild disease course.”

*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.