Superior immunogenicity of mRNA over adenoviral vectored COVID-19 vaccines reflects B cell dynamics independent of anti-vector immunity: Implications for future pandemic vaccines
Authors:
- Liu, Yi
- Sánchez-Ovando, Stephany
- Carolan, Louise
- Dowson, Leslie
- Khvorov, Arseniy
- Jessica Hadiprodjo, A.
- Tseng, Yeu Yang
- Delahunty, Catherine
- Khatami, Ameneh
- Macnish, Marion
- Dougherty, Sonia
- Hagenauer, Michelle
- Riley, Kathryn E.
- Jadhav, Ajay
- Harvey, Joanne
- Kaiser, Marti
- Mathew, Suja
- Hodgson, David
- Leung, Vivian
- Subbarao, Kanta
- Cheng, Allen C.
- Macartney, Kristine
- Koirala, Archana
- Marshall, Helen
- Clark, Julia
- Blyth, Christopher C.
- Wark, Peter
- Kucharski, Adam J.
- Sullivan, Sheena G.
- Fox, Annette
Details:
Vaccine, Volume 41, Issue 48, 2023-11-22
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Both vector and mRNA vaccines were an important part of the response to the COVID-19 pandemic and may be required in future outbreaks and pandemics. The aim of this study was to validate whether immunogenicity differs for adenoviral vectored (AdV) versus mRNA vaccines against SARS-CoV-2, and to investigate how anti-vector immunity and B cell dynamics modulate immunogenicity. We enrolled SARS-CoV-2 infection-naïve health care workers who had received two doses of either AdV AZD1222 (n = 184) or mRNA BNT162b2 vaccine (n = 274) between April and October 2021. Blood was collected at least once, 10–48 days after vaccine dose 2 for antibody and B cell analyses. Median ages were 42 and 39 years, for AdV and mRNA vaccinees, respectively. Surrogate virus neutralization test (sVNT) and spike binding antibody titres were a median of 4.2 and 2.2 times lower, respectively, for AdV compared to mRNA vaccinees (p < 0.001). Median percentages of memory B cells that recognized fluorescent-tagged spike and RBD were 2.9 and 8.3 times lower, respectively for AdV compared to mRNA vaccinees. Titres of IgG reactive with human adenovirus type 5 hexon protein rose a median of 2.2-fold after AdV vaccination but were not correlated with anti-spike antibody titres. Together the results show that mRNA induced substantially more sVNT antibody than AdV vaccine, which reflected greater B cell expansion and targeting of the RBD rather than an attenuating effect of anti-vector antibodies. ClinicalTrials.gov Identifier: NCT05110911.