mRNA-based and adenoviral vector-based COVID-19 vaccines elicit diverse humoral immunity

Scientists from the USA have recently compared the dynamics of humoral and cellular immune responses induced by mRNA-based and adenoviral vector-based coronavirus disease 2019 (COVID-19) vaccines. The findings reveal a difference in humoral immune responses. The study is currently available on the medRxiv* preprint server.


In the USA, three COVID-19 vaccines have been approved by the US Food and Drug Administration (FDA), with mRNA-1273 (Moderna) and Ad26.COV2.S (Johnson and Johnson-Janssen) having emergency use approval and BNT162b2 (BioNTech-Pfizer) having full approval. While mRNA-1273 and BNT162b2 are mRNA-based two-dose vaccines against COVID-19, Ad26.COV2.S is an adenoviral vector-based single-dose vaccine. Studies conducted in the real-world setups have shown that these vaccines are highly effective in preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe COVID-19.

However, some recent studies have revealed that breakthrough infections can occur in fully vaccinated individuals due to the emergence of novel viral variants with spike mutations that are resistant to vaccine-induced antibodies. Another reason could be waning vaccine immunity with time. This highlights the importance of studying the robustness and durability of immune responses elicited by currently available COVID-19 vaccines.   

In the current study, the scientists have compared the humoral and cellular immune responses elicited by mRNA-based and adenoviral vector-based COVID-19 vaccines in SARS-CoV-2-naïve individuals.

Study design

The study was conducted on a total of 33 individuals, of whom 17 received adenoviral vector-based vaccines and 16 received mRNA-based vaccines.

The plasma samples collected from all vaccine recipients were analyzed for spike receptor binding domain (RBD)-specific binding and neutralizing antibodies. The durability of vaccine-induced humoral response was evaluated by estimating the frequency of RBD-specific memory B cells.  

To evaluate the cellular immune response, peripheral blood mononuclear cells were isolated from the vaccine recipients and analyzed for spike-specific, interferon-gamma-secreting T cells.

Important observations

The study findings revealed that the levels of anti-RBD binding and neutralizing antibodies are significantly higher in individuals immunized with mRNA vaccines compared to that in individuals immunized with adenoviral vector-based vaccines.

Despite marked differences in vaccine-induced antibody responses, no significant difference in RBD-specific B cell frequencies and interferon-gamma-secreting T cell levels was observed between mRNA-vaccinated and adenoviral vector-vaccinated individuals.

Study significance

Collectively, the study findings reveal that compared to Johnson & Johnson-developed adenoviral vector-based COVID-19 vaccine, Pfizer- and Moderna-developed mRNA-based vaccines induce higher levels of anti-SARS-CoV-2 binding and neutralizing antibodies on average 5 months after immunization. However, all tested vaccines perform equivalently in terms of inducing antigen-specific memory B cell and T cell responses.

It is generally considered that humoral immunity provides rapid protection against symptomatic infection by controlling viral replication. In contrast, memory immune cells (B cells and T cells) that take a relatively longer time to be expressed after vaccination play the central role in providing long-term protection against severe disease.

Thus, the difference in vaccine-induced humoral and cellular immune responses observed in the study justifies the reported evidence on waning vaccine immunity against symptomatic breakthrough infections. Moreover, it explains the fact that COVID-19 vaccines are capable of providing long-lasting protection against severe COVID-19 and related hospitalization.

Given the current observations, the scientists suggest that additional booster doses of the vaccines, especially adenoviral vector-based vaccines, might be important to induce robust protection against symptomatic SARS-CoV-2 infection. However, these booster doses might not provide additional protection against hospitalization and mortality.

In this context, it is worth mentioning that according to the interim data provided by Johnson & Johnson, a second dose of the Ad26.COV2.S vaccine is predicted to induce more robust antibody responses compared to the primary dose.

*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.

Journal reference:
Dr. Sanchari Sinha Dutta

Written by

Dr. Sanchari Sinha Dutta

Dr. Sanchari Sinha Dutta is a science communicator who believes in spreading the power of science in every corner of the world. She has a Bachelor of Science (B.Sc.) degree and a Master's of Science (M.Sc.) in biology and human physiology. Following her Master's degree, Sanchari went on to study a Ph.D. in human physiology. She has authored more than 10 original research articles, all of which have been published in world renowned international journals.


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