I read with surprise that Bansel et al. (1) detected the exosomal spike protein (S2) of SARS-CoV-2 in the vaccinee's plasma 4 mo after vaccination of BNT162b2. There are notable caveats in their analysis; first, the authors used the precipitation-based commercial kit for the exosome isolation, which leads to the contamination of nonexosome materials (2) that could have compromised the quality of Western blotting. In addition, the details of the Ab against spike protein are not provided in the article, which is critical to verify the validity of the Western blotting.

Second, the authors stated that S2 proteins were found from day seven to 4 mo after the first vaccination. This is not in line with another report that demonstrated the presence of spike S1 in the plasma immediately after vaccination (mRNA-1273), but barely detected them on day 14 and beyond (3). Although the discrepancy in the kinetics could be explained by the different target (exosomal S2 versus S1/spike in plasma) or assay (Western blotting versus Simoa assay), Ogata et al. appear to be more convincing because of the quantitativeness of the detection method (3).

The biological expectation is that mRNA vaccines are translated to the Ag and immediately degraded. It is highly unlikely that mRNA vaccines remain for several months and continuously produce Ags. The short duration of the functionality of the mRNA vaccine was already reported. Further clarification and justification would be warranted to resolve these concerns and convince the readers.

1.
Bansal
S.
,
S.
Perincheri
,
T.
Fleming
,
C.
Poulson
,
B.
Tiffany
,
R. M.
Bremner
,
T.
Mohanakumar
.
2021
.
Cutting edge: circulating exosomes with COVID spike protein are induced by BNT162b2 (Pfizer–BioNTech) vaccination prior to development of antibodies: a novel mechanism for immune activation by mRNA vaccines.
J. Immunol.
207
:
2405
2410
.
2.
Patel
G. K.
,
M. A.
Khan
,
H.
Zubair
,
S. K.
Srivastava
,
M.
Khushman
,
S.
Singh
,
A. P.
Singh
.
2019
.
Comparative analysis of exosome isolation methods using culture supernatant for optimum yield, purity and downstream applications.
Sci. Rep.
9
:
5335
.
3.
Ogata
A. F.
,
C.-A.
Cheng
,
M.
Desjardins
,
Y.
Senussi
,
A. C.
Sherman
,
M.
Powell
,
L.
Novack
,
S.
Von
,
X.
Li
,
L. R.
Baden
,
D. R.
Walt
.
2022
.
Circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine antigen detected in the plasma of mRNA-1273 vaccine recipients.
Clin. Infect. Dis.
74
:
715
718
.