mRNA booster vaccines may be a good investment in developing countries

“Our results indicate that one booster shot of an mRNA vaccine, as a complement to the cheaper but less effective inactivated vaccines, is sufficient to achieve the ‘gold-standard’ immune response measured after three doses of mRNA vaccine,” says Qiang Pan Hammarström, professor at the Department of Biosciences and Nutrition, Karolinska Institutet, who led the study. “That would likely be a good investment even in resource-poor countries to protect against severe COVID-19.”

The study included 175 healthy volunteers with different vaccination histories. The researchers investigated the presence of antibodies and memory B and T cell responses against SARS-CoV-2 after vaccination and booster shots with an inactivated vaccine (Sinovac/Sinopharm), mRNA vaccine (Pfizer-BioNTech/Moderna), or a combination of both.

The results showed that a booster shot of an mRNA vaccine to individuals who had received two doses of inactivated vaccine strongly augmented the levels of neutralising antibodies and memory B and T cells directed against SARS-CoV-2 variants of concern, including Omicron. The levels were markedly higher than that of people receiving three doses of inactivated vaccine, and similar to that in individuals receiving three doses of mRNA vaccine or a boost of mRNA vaccine after natural infection.

“Given that almost half of the COVID-19 vaccine doses distributed worldwide are inactivated vaccines, an improved mRNA booster strategy may benefit billions of people in our fight against emerging variants of concern,” says Qiang Pan Hammarström. “A more widespread use of mRNA booster shots may also help China to overcome their current lockdowns.”

A limitation of the study is the relatively low number of participants; only 16 individuals received vaccination with two doses of inactivated vaccine followed by an mRNA vaccine boost. Moreover, the median age of the study participants was 36 years of age, which is younger than the average global population. Hence, the results need to be confirmed in large-scale longitudinal studies that include different age groups.

The researchers will now continue to study the effect of the heterologous vaccination strategy on emerging variants of the SARS-CoV-2 virus.

“We will for the first time evaluate if this vaccination strategy can neutralise the two emerging Omicron subvariants BA.4 and BA.5, underlying the new wave of COVID-19 in South Africa,” says Qiang Pan Hammarström.

The study was conducted within the research consortium ATAC, funded by the European Commission in response to the COVID-19 pandemic and coordinated by Karolinska Institutet. Other members of the consortium include the Institute for Research in Biomedicine (Switzerland), Policlinico San Matteo in Pavia (Italy), Technische Universitaet Braunschweig (Germany) and the Joint Research Centre of the European Commission. Collaborations with Stockholm University (Sweden), Tehran University of Medical Sciences (Iran), Shahid Beheshti University of Medical Sciences (Iran), and Peking University Health Science Center (China) were also instrumental in the realisation of the study.

The study was also funded by the Swedish Research Council and the Knut and Alice Wallenberg Foundation. The researchers declare no competing interests.

Publication: "Heterologous immunization with inactivated vaccine followed by mRNA-booster elicits strong immunity against SARS-CoV-2 Omicron variant”. Fanglei Zuo, Hassan Abolhassani, Likun Du, Antonio Piralla, Federico Bertoglio, Leire de Campos-Mata, Hui Wan, Maren Schubert, Irene Cassaniti, Yating Wang, Josè Camilla Sammartino, Rui Sun, Stelios Vlachiotis, Federica Bergami, Makiko Kumagai-Braesch, Juni Andréll, Zhaoxia Zhang, Yintong Xue, Esther Veronika Wenzel, Luigi Calzolai, Luca Varani, Nima Rezaei, Zahra Chavoshzadeh, Fausto Baldanti, Michael Hust, Lennart Hammarström, Harold Marcotte, and Qiang Pan-Hammarström. Nature Communications, online 13 May 2022, doi: 10.1038/s41467-022-30340-5.