There is an immune response to the components of the vaccine vector along with a response to the SARS-CoV-2 antigen.  However, there is no cross-reactivity between the components, meaning that the administration of rAd5 doesn't increase levels of neutralising antibodies to rAd26 and vice versa.  Therefore, priming with rAd26 will not affect the RBD-specific antibodies that are produced against SARS-CoV-2.  

Bowdoin College

The phase 1/2 clinical studies evaluating the safety and immunogenicity of the heterologous rAd26 and rAd5 vector-based COVID-19 vaccine reported outcomes across several key areas. These primary results included the evaluation of adverse effects, the cell-mediated (T-cell) immune response to the SARS-CoV-2 glycoprotein, the humoral immune response encompassing RBD-specific IgG and neutralizing antibodies, and the specific neutralizing antibody response to the rAd26 and rAd5 viral vectors.

Results of rAd26 and rAd5 Vector-Based Vaccine Phase 1/2 Studies

Logunov, D., Dolzhikova, I., et. al. "Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine in two formulations: two open, non-randomised phase 1/2 studies from Russia."  The Lancet, vol 396, 4 Sept. 2020, pp. 887-897. https://doi.org/10.1016/S0440-6736(20)31866-3.


Safety and immunogenicity of an rAd26 and rAd5
vector-based heterologous prime-boost COVID-19 vaccine in two formulations: two open, non randomised phase 1/2 studies from Russia

The most common systemic and local reactions were pain at injection site (44, 58%), hyperthermia (38, 50%), headache (32, 42%), asthenia (21, 28%), and muscle and joint pain (18, 24%). In volunteers who received both vaccine components (rAd26-S and rAd5-S), most adverse events occurred after the second vaccination. 

Adverse effects of rAd-26 and rAd-5 

Antigen-specific cells of both T-helper (CD4+) and T-killer (CD8+) cells are formed after the injection of the two components separately in phase 1 and together in phase 2.  There is also an increase in the concentration of interferon-γ secretion in peripheral blood mononuclear cells after injection in 100% of volunteers.

Cell-mediated (T-cell) immune response 

In phase 1 (A and C) SARS-CoV-2 RBD-specific IgG antibodies were detected on day 14 in 88.9% of participants injected with only rAd26-S and in 84.2% of participants with rAd5-S.  At day 21, RBD-specific IgG  were detected in all participants.

In phase 2 (B and D) SARS-CoV-2 RBD-specific IgG antibodies were detected in 85% of participants on day 14 and in 100% on day 21.  The boosting component (rAd5) led to an increase in IgG titres.  100% of participants produced neutralising antibodies to SARS-CoV-2 with both rAd26-S and rAd5-S.  

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