Dynamics of humoral and cellular immune responses after homologous and heterologous SARS-CoV-2 vaccination with ChAdOx1 nCoV-19 and BNT162b2
Authors: Vogel Emanuel , Kocher Katharina , Priller Alina , Cheng Cho-Chin , Steininger Philipp , Liao Bo-Hung , Körber Nina , Willmann Annika , Irrgang Pascal , Held Jürgen , Moosmann Carolin , Schmidt Vivianne , Beileke Stephanie , Wytopil Monika , Heringer Sarah , Bauer Tanja , Brockhoff Ronja , Jeske Samuel , Mijocevic Hrvoje , Christa Catharina , Salmanton-García Jon , Tinnefeld Kathrin , Bogdan Christian , Yazici Sarah , Knolle Percy , Cornely Oliver A. , Überla Klaus , Protzer Ulrike , Schober Kilian , Tenbusch Matthias 
Published: March 2022

Vaccines are the most important means to overcome the SARS-CoV-2 pandemic. They induce specific antibody and T-cell responses but it remains open how well vaccine-induced immunity is preserved over time following homologous and heterologous immunization regimens. Here, we compared the dynamics of humoral and cellular immune responses up to 5 months after homologous or heterologous vaccination with either ChAdOx1-nCoV-19 (ChAd) or BNT162b2 (BNT) or both. Antibody responses significantly waned after vaccination, irrespective of the regimen. The capacity to neutralize SARS-CoV-2 – including variants of concern such as Delta or Omicron – was superior after heterologous compared to homologous BNT vaccination, both of which resulted in longer-lasting humoral immunity than homologous ChAd immunization. T-cell responses showed less waning irrespective of the vaccination regimen. These findings demonstrate that heterologous vaccination with ChAd and BNT is a potent approach to induce long-term humoral and cellular immune protection.

Research in context

Evidence before this study

Due to some rare severe side effects after the administration of the adenoviral vaccine, ChAdOx1 nCoV-19, many countries recommended a heterologous vaccination scheme including mRNA vaccines like BNT162b2 for the second dose. We performed a PubMed search (with no restrictions on time span) using the search terms “SARS-CoV-2” and “heterologous vaccination” and obtained 247 results. Only a fraction of manuscripts included direct comparisons of patient cohorts that received either a heterologous or a homologous vaccination regimen. Of those, the vast majority investigated only short-term immunogenicity after vaccination. Thus, little is known about the long-term maintenance of immunity by heterologous compared to homologous vaccination.

Added value of this study

We add a very comprehensive and comparative study investigating heterologous and homologous vaccination regimens early and late after vaccination. Key features include the number of patients (n = 473), the number of vaccination cohorts (n= 3), the fact that samples were derived from three independent study centers and comparative analyses were performed at two independent study centers, as well as in-depth investigation of humoral and T cellular immunity.

Implications of all the available evidence

The recent data creates a line of evidence that heterologous vaccination, compared to homologous vaccination regimens, results in at least non-inferior maintenance of humoral and cellular immunity. The enhanced understanding of immunity induced by individual vaccination regimens is crucial for further recommendations regarding the necessity, timing and choice of additional vaccinations and public health policies.