Heterologous prime-boost immunization with AstraZeneca and Pfizer COVID-19 vaccines safe and well-tolerated, study finds

A team of scientists from Germany has recently evaluated the reactogenicity profile of heterologous ChAdOx1 nCoV-19/BNT162b2 prime-boost vaccination among healthcare workers. The findings reveal that a 12-week interval regimen of heterologous vaccination is well-tolerated among participants. The study is currently available on the medRxiv* preprint server.

Background

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is by far the largest pandemic in modern history, with over 167 million confirmed infections and more than 3.4 million deaths worldwide. The only possible way to control the pandemic is rapid and widespread vaccination. To meet the increasing demand for vaccines or to overcome vaccine shortages, heterologous prime-boost vaccination is becoming the topic of international interest.

Because of rare blood clotting events associated with the Oxford-AstraZeneca COVID-19 vaccine (ChAdOx1 nCoV-19), healthcare advisory bodies of many countries are now recommending that people previously vaccinated with ChAdOx1 nCoV-19 should receive a second booster dose of most preferably mRNA-based vaccines, such as BNT162b2 (Pfizer-BioNTech). However, not enough data is currently available on the immunogenicity, reactogenicity, and safety of heterologous prime-boost vaccination regimen.

In the current study, the scientists have investigated the reactogenicity of homologous BNT162b2/BNT162b2 and heterologous ChAdOx1 nCoV-19/BNT162b2 prime-boost vaccination regimens in a group of 326 healthcare workers from Berlin, Germany.  

Study design

In the entire study cohort, the reactogenicity data after the first vaccination with BNT162b2 or ChAdOx1 nCoV-19 were available for 178 and 148 participants, respectively. Similarly, the reactogenicity data after homologous BNT162b2/BNT162b2 and heterologous ChAdOx1 nCoV-19/BNT162b2 prime-boost vaccinations were available for 159 and 71 participants, respectively.

In the heterologous ChAdOx1 nCoV-19/BNT162b2 prime-boost vaccination group, two doses of respective vaccines were administered at an interval of 12 weeks.

The US Food and Drug Administration (FDA) modified criteria were used to grade vaccine-associated reactogenicity.

Important observations

No significant difference in frequency or severity of local reactions was observed after homologous or heterologous prime-boost vaccination. However, considerable differences in systemic reactions were observed between the tested vaccination regimens. The most frequent systemic reactions were observed after prime vaccination with ChAdOx1 nCoV-19 (86%), followed by homologous BNT162b2/BNT162b2 (65%) and heterologous ChAdOx1 nCoV-19/BNT162b2 (48%) prime-boost vaccinations.  

Compared to heterologous ChAdOx1 nCoV-19/BNT162b2 prime-boost vaccination, ChAdOx1 nCoV-19 prime vaccination was associated with more frequent severe systemic reactions including fatigue, myalgia, headache, chills, and high fever. The highest intake of antipyretic medicines was observed before (protective) and after (curative) ChAdOx1 nCoV-19 prime vaccination. In contrast, significantly lower consumption of antipyretic medicines was observed among participants belonging to other vaccination groups.

Study significance

The study findings reveal comparable reactogenicity for homologous BNT162b2/BNT162b2 and heterologous ChAdOx1 nCoV-19/BNT162b2 prime-boost vaccinations. Among study participants, heterologous prime-boost vaccination exhibits a well-tolerated profile.

Based on the study findings, the scientists recommend that immunizing people with the 1^st dose of ChAdOx1 nCoV-19 vaccine and 2^nd dose of BNT162b2 vaccine at an interval of 12 weeks can significantly reduce vaccine-associated reactogenicity.

*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. 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.