Critical considerations for COVID-19 vaccines and possibilities for rational

improvement

by Paolo Zanotto, D.PHIL.1¶ and Peter A. McCullough, MD, MPH2

1¶. Laboratory of Molecular Evolution & Bioinformatics (LEMB), Department of Microbiology,

Biomedical Sciences Institute (ICB II), University of São Paulo (USP), Av. Prof. Lineu Prestes, nº
1374 São Paulo, SP, Brazil, CEP 05508-000. [email protected]
2. Truth for Health Foundation, Tucson, AZ 85728, USA. [email protected]
¶
Corresponding author

“These facts may indicate a conceptual blunder of an immunization strategy that, by

design, inhibits the same very response it was supposed to induce”

In a natural SARS-CoV-2 infection there is viral replication for around two weeks 1 in
which, at least 25 immunogenic viral proteins are presented 2 to the host immune
system, eliciting cellular and both mucosal serum antibody responses. But in the
current gene expression-based adenoviral and mRNA vaccines, there is only spike
presentation produced in several tissues unnecessarily and has been associated 3 with
several serious adverse effects, such as myocarditis in adolescents and young adults.

To help the vaccine mRNA evade 4 the innate immune system, all uracil bases have, by
design, been replaced by pseudouridines (y). This has a, perhaps unintended, role in
preventing degradation by ribonucleases, and the poly-A 3' includes a GC rich domain
inside a 100 bp-long poly-A tail 5 , hampering degradation by 3'-exonucleases, making
this mRNA ‘quasi non-biodegradable’. Possibly, therefore, the vaccine mRNA ended up
lasting for a minimum of 2 months 6 in germinal centers (GC) of the lymph nodes, in
opposition of natural mRNAs that have a turn-over time that last 9-10 hours on
average. It is worth mentioning that only a small percentage of cellular RNAs have a
very small number of bases being y-modified after transcription, for increased stability
to improve functional inter-molecular interactions 7. So, it becomes a possibly
unreasonable option to design a AyGC molecule for which, unwanted implications
were observed following a hurried population-level administration strategy. Why for
the sake of safety, when expediency was at stake, time-tried, inactivated virus vaccine,
with cross-linked but exposed structural proteins platforms, were not prioritized to
start with, followed by attenuated platforms?

It is worthwhile discussing some of the problems with the current platforms that share
the inherent complications and challenges of gene therapy. The spike is continuously
produced and spread to tissues beyond the injection site. This was shown in a series of
Biopsies of lethal cases of vaccine adverse effects 8. Its only product – complete spike
glycoprotein – and its subproducts, were found to be secreted from cells transfected
by the vaccine mRNA, via exosomes produced in the secretory pathway. The spike is
presented in exosomes as in a virus-like particle (VLP), fusing with endothelial cells, via
its binding with ACE2 and CD147 receptors 9. This is likely to agglutinate RBCs (which
also have CD147, besides ACE2), possibly, in some cases nucleating clots associated
with acute ischemic stroke due to mechanical thrombectomy and myocardial
infarction 10.
The consequences of the bio magnification of spike-presenting VLP-like exosomes, the
offspring of the mRNA vaccine, was studied in quite detail 11. It was shown by electron
microscopy to present spike in a similar transmembrane fashion as the actual virion,
while mass spectrometry indicated that both S1, including the receptor binding
domain (RBD), and S2 domains are present as well as complete spike protein.
Moreover, the secreted spike proteins inhibited the neutralization from antibodies, in
a similar manner as defective, sub-particles do HIV and HBV do as a decoy to evade our
immunity. This was also shown in assays using convalescent sera 11 .

These facts may indicate a conceptual blunder of an immunization strategy that, by

design, inhibits the same very response it was supposed to induce. In all it is a
devastating outcome, considering that, based on Jason McLellan’s ideas and previous
work 12, the spike protein expressed on vaccines was locked 13, in a pre-fusion
conformation via the insertion of two proline 14 amino acids and, should therefore have
no fusogenic capabilities. Although the idea was clever, possibly deleterious activities
of the S1 and S2 domains were not fully accounted for. Unfortunately, the S1 domain
of spike was shown to persist in CD16+ Monocytes up to 15 months 15 post-infection in
patients suffering of Post-Acute Sequelae of COVID-19 (PASC), in the absence of the
detection of complete viral genomes. These facts hint to the notion that a full
“stabilized” spike does not do the job and causes problems and, that the RBD alone
may be a safer option for a better improved vaccine.

Immunohistochemistry/immunocytochemistry studies 16 with autopsy material show

spike near the endothelia in several tissues. The indication that this is a consequence
of the vaccine is the lack of reaction with anti-N (nucleoprotein) antibodies, which
would incriminate the virus, exception made to inactivated vaccines that expose virion
contents during its preparation, which was not the case with those patients.

Moreover, spike causes undesirable inflammatory responses 17, interferes with the cell
DNA integrity 18 and causes mitochondrial dysfunction 19 associated with the COVID
induced neuropathology. Moreover, the extensive list of observed events suggests
comprehensive tissue injury (via ACE2), severe vasculitis and coagulopathies (via ACE2
and CD147). Nevertheless, the intranasal administration of spike S1 domain was shown
to kill cancer cells in mice 20 , but one would like to see the same type of experiments
done in healthy tissues as a control. Given the S1 impact in PASC, we need to consider
if its suggested therapeutic use makes any sense. Indeed, it would also be necessary to
question a vaccine said to be designed in a few hours in a single day 21 , making use of a
synthetic mRNA designed to be almost "non-biodegradable" that has a half-life way
greater than that of the detection time of viral genomic RNA, of about two weeks 22
and, that possibly bio magnifies spike for unreasonably longer periods of time and in
quantities incompatible with that of a natural acute infection.

One could argue that the design of a spike-centered vaccine strategy in the human
system, does not follow what would be expected from a natural acute infection and is
seriously conceptually flawed. Notwithstanding, the criticisms raised herein have been
put forward already by the tour de force of Seneff and Nigh 23 and by Altman 24, among
 others, in a more thorough and detailed way. Sadly, the worldwide impact of the
accumulation of serious adverse reactions, low risk benefit ratio, deaths and excess
deaths associated with the in vivo gene-expression vaccine platforms deployed, has
helped deconstruct the reputation of important and effective vaccines such as
smallpox, yellow fever, polio, measles, &c 25–29. This is made even worse, when most
corporative media and even scientific journals, prefer to discredit any criticism,
hijacking the issue away from the true, necessary scientific debate.

Why not use epitopes of the nucleoprotein (N), which induces comprehensive
neutralizing cross-reaction between different clades of endemic betacoronaviruses and
include epitopes of the membrane protein M and the envelope protein (E), which
could prevent its apparent role in the cytokine storm following natural infection 30,31 ?
Both structural proteins and several others would present additional promising, non-
spike antigens for future prophylactic vaccines against COVID-19. Moreover, why not
present only multimers of the spike's loop 2, containing the receptor binding domain
(RBD) 32,33 ? This was shown to have increased immunogenicity and to reduce adverse
effects in preclinical phase studies in other SARS viruses 34 . Crucially, why not consider
strategies including nasal mist administration that are known to cause much needed
mucosal antibody response via IgA, to break the chain of transmission, the lack of
which, besides adverse effects, has been an obvious, glaring and demoting non
sequitur of the current gene-expression vaccines 35 ?

We believe that these aspects should be openly discussed by the scientific community
and not suppressed in the way that it has been done by institutions, the press and by
people without specific technical background. A better, safer vaccine for SARS-CoV-2 is
possible, if the issue is dealt with in a more comprehensive manner considering cellular
and antibody mediated immunity with the understanding that multiple epitopes must
be engaged given the high mutagenic potential of SARS-CoV-2 and the failure of Spike
protein-only based vaccines.

ACKNOWLEDGMENTS

We thank, the colleagues that gave opinions and suggestions to the text and Dr. Flavia
P. Zanotto from Escrever Ciência (www.escreverciencia.com) for her voluntary
assistance in the editorial preparation.

REFERENCES

(1) Walsh, K. A.; Jordan, K.; Clyne, B.; Rohde, D.; Drummond, L.; Byrne, P.; Ahern, S.; Carty,
P. G.; O’Brien, K. K.; O’Murchu, E.; O’Neill, M.; Smith, S. M.; Ryan, M.; Harrington, P.
SARS-CoV-2 Detection, Viral Load and Infectivity over the Course of an Infection. J
Infect 2020, 81 (3), 357. https://doi.org/10.1016/J.JINF.2020.06.067.
(2) Grifoni, A.; Weiskopf, D.; Ramirez, S. I.; Mateus, J.; Dan, J. M.; Moderbacher, C. R.;
Rawlings, S. A.; Sutherland, A.; Premkumar, L.; Jadi, R. S.; Marrama, D.; de Silva, A. M.;
Frazier, A.; Carlin, A. F.; Greenbaum, J. A.; Peters, B.; Krammer, F.; Smith, D. M.; Crotty,
S.; Sette, A. Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans with
 COVID-19 Disease and Unexposed Individuals. Cell 2020, 181 (7), 1489-1501.e15.
https://doi.org/10.1016/J.CELL.2020.05.015.
(3) Yonker, L. M.; Swank, Z.; Bartsch, Y. C.; Burns, M. D.; Kane, A.; Boribong, B. P.; Davis, J.
P.; Loiselle, M.; Novak, T.; Senussi, Y.; Cheng, C.-A.; Burgess, E.; Edlow, A. G.; Chou, J.;
Dionne, A.; Balaguru, D.; Lahoud-Rahme, M.; Arditi, M.; Julg, B.; Randolph, A. G.; Alter,
G.; Fasano, A.; Walt, D. R. Circulating Spike Protein Detected in Post–COVID-19 MRNA
Vaccine Myocarditis. Circulation 2023, 147 (11), 867–876.
https://doi.org/10.1161/circulationaha.122.061025.
(4) Karikó, K.; Buckstein, M.; Ni, H.; Weissman, D. Suppression of RNA Recognition by Toll-
like Receptors: The Impact of Nucleoside Modification and the Evolutionary Origin of
RNA. Immunity 2005, 23 (2), 165–175. https://doi.org/10.1016/j.immuni.2005.06.008.
(5) Seneff, S.; Nigh, G. Worse Than the Disease? Reviewing Some Possible Unintended
Consequences of the MRNA Vaccines Against COVID-19. International Journal of
Vaccine Theory, Practice, and Research 2021, 2 (1).
https://doi.org/10.56098/ijvtpr.v2i1.
(6) Röltgen, K.; Nielsen, S. C. A.; Silva, O.; Younes, S. F.; Zaslavsky, M.; Costales, C.; Yang, F.;
Wirz, O. F.; Solis, D.; Hoh, R. A.; Wang, A.; Arunachalam, P. S.; Colburg, D.; Zhao, S.;
Haraguchi, E.; Lee, A. S.; Shah, M. M.; Manohar, M.; Chang, I.; Gao, F.; Mallajosyula, V.;
Li, C.; Liu, J.; Shoura, M. J.; Sindher, S. B.; Parsons, E.; Dashdorj, N. J.; Dashdorj, N. D.;
Monroe, R.; Serrano, G. E.; Beach, T. G.; Chinthrajah, R. S.; Charville, G. W.; Wilbur, J.
L.; Wohlstadter, J. N.; Davis, M. M.; Pulendran, B.; Troxell, M. L.; Sigal, G. B.; Natkunam,
Y.; Pinsky, B. A.; Nadeau, K. C.; Boyd, S. D. Immune Imprinting, Breadth of Variant
Recognition, and Germinal Center Response in Human SARS-CoV-2 Infection and
Vaccination. Cell 2022, 185 (6), 1025-1040.e14.
https://doi.org/10.1016/j.cell.2022.01.018.
(7) Xu, J.; Gu, A. Y.; Thumati, N. R.; Wong, J. M. Y. Quantification of Pseudouridine Levels in
Cellular RNA Pools with a Modified HPLC-UV Assay. Genes 2017, Vol. 8, Page 219 2017,
8 (9), 219. https://doi.org/10.3390/GENES8090219.
(8) Baumeier, C.; Aleshcheva, G.; Harms, D.; Gross, U.; Hamm, C.; Assmus, B.; Westenfeld,
R.; Kelm, M.; Rammos, S.; Wenzel, P.; Münzel, T.; Elsässer, A.; Gailani, M.; Perings, C.;
Bourakkadi, A.; Flesch, M.; Kempf, T.; Bauersachs, J.; Escher, F.; Schultheiss, H. P.
Intramyocardial Inflammation after COVID-19 Vaccination: An Endomyocardial Biopsy-
Proven Case Series. International Journal of Molecular Sciences 2022, Vol. 23, Page
6940 2022, 23 (13), 6940. https://doi.org/10.3390/IJMS23136940.
(9) Wang, K.; Chen, W.; Zhou, Y.-S.; Lian, J.-Q.; Zhang, Z.; Du, P.; Gong, L.; Zhang, Y.; Cui,
H.-Y.; Geng, J.-J.; Wang, B.; Sun, X.-X.; Wang, C.-F.; Yang, X.; Lin, P.; Deng, Y.-Q.; Wei,
D.; Yang, X.-M.; Zhu, Y.-M.; Zhang, K.; Zheng, Z.-H.; Miao, J.-L.; Guo, T.; Shi, Y.; Zhang, J.;
Fu, L.; Wang, Q.-Y.; Bian, H.; Zhu, P.; Chen, Z.-N. SARS-CoV-2 Invades Host Cells via a
Novel Route: CD147-Spike Protein. bioRxiv 2020, 2020.03.14.988345.
https://doi.org/10.1101/2020.03.14.988345.
(10) De Michele, M.; d’Amati, G.; Leopizzi, M.; Iacobucci, M.; Berto, I.; Lorenzano, S.;
Mazzuti, L.; Turriziani, O.; Schiavo, O. G.; Toni, D. Evidence of SARS-CoV-2 Spike Protein
on Retrieved Thrombi from COVID-19 Patients. J Hematol Oncol 2022, 15 (1), 1–5.
https://doi.org/10.1186/S13045-022-01329-W/TABLES/1.
(11) Troyer, Z.; Alhusaini, N.; Tabler, C. O.; Sweet, T.; de Carvalho, K. I. L.; Schlatzer, D. M.;
Carias, L.; King, C. L.; Matreyek, K.; Tilton, J. C. Extracellular Vesicles Carry SARS-CoV-2
 Spike Protein and Serve as Decoys for Neutralizing Antibodies. J Extracell Vesicles 2021,
10 (8), e12112. https://doi.org/10.1002/JEV2.12112.
(12) Mukhamedova, M.; Wrapp, D.; Shen, C. H.; Gilman, M. S. A.; Ruckwardt, T. J.;
Schramm, C. A.; Ault, L.; Chang, L.; Derrien-Colemyn, A.; Lucas, S. A. M.; Ransier, A.;
Darko, S.; Phung, E.; Wang, L.; Zhang, Y.; Rush, S. A.; Madan, B.; Stewart-Jones, G. B. E.;
Costner, P. J.; Holman, L. S. A.; Hickman, S. P.; Berkowitz, N. M.; Doria-Rose, N. A.;
Morabito, K. M.; DeKosky, B. J.; Gaudinski, M. R.; Chen, G. L.; Crank, M. C.; Misasi, J.;
Sullivan, N. J.; Douek, D. C.; Kwong, P. D.; Graham, B. S.; McLellan, J. S.; Mascola, J. R.
Vaccination with Prefusion-Stabilized Respiratory Syncytial Virus Fusion Protein
Induces Genetically and Antigenically Diverse Antibody Responses. Immunity 2021, 54
(4), 769-780.e6. https://doi.org/10.1016/j.immuni.2021.03.004.
(13) Hsieh, C. L.; Goldsmith, J. A.; Schaub, J. M.; DiVenere, A. M.; Kuo, H. C.; Javanmardi, K.;
Le, K. C.; Wrapp, D.; Lee, A. G.; Liu, Y.; Chou, C. W.; Byrne, P. O.; Hjorth, C. K.; Johnson,
N. V.; Ludes-Meyers, J.; Nguyen, A. W.; Park, J.; Wang, N.; Amengor, D.; Lavinder, J. J.;
Ippolito, G. C.; Maynard, J. A.; Finkelstein, I. J.; McLellan, J. S. Structure-Based Design of
Prefusion-Stabilized SARS-CoV-2 Spikes. Science (1979) 2020, 369 (6509), 1501–1505.
https://doi.org/10.1126/SCIENCE.ABD0826/SUPPL_FILE/ABD0826_HSIEH_SM.PDF.
(14) Sanders, R. W.; Moore, J. P. Virus Vaccines: Proteins Prefer Prolines. Cell Host Microbe
2021, 29 (3), 327–333. https://doi.org/10.1016/J.CHOM.2021.02.002.
(15) Patterson, B. K.; Francisco, E. B.; Yogendra, R.; Long, E.; Pise, A.; Rodrigues, H.; Hall, E.;
Herrera, M.; Parikh, P.; Guevara-Coto, J.; Triche, T. J.; Scott, P.; Hekmati, S.; Maglinte,
D.; Chang, X.; Mora-Rodríguez, R. A.; Mora, J. Persistence of SARS CoV-2 S1 Protein in
CD16+ Monocytes in Post-Acute Sequelae of COVID-19 (PASC) up to 15 Months Post-
Infection. Front Immunol 2022, 12, 5526.
https://doi.org/10.3389/FIMMU.2021.746021/BIBTEX.
(16) Baumeier, C.; Aleshcheva, G.; Harms, D.; Gross, U.; Hamm, C.; Assmus, B.; Westenfeld,
R.; Kelm, M.; Rammos, S.; Wenzel, P.; Münzel, T.; Elsässer, A.; Gailani, M.; Perings, C.;
Bourakkadi, A.; Flesch, M.; Kempf, T.; Bauersachs, J.; Escher, F.; Schultheiss, H. P.
Intramyocardial Inflammation after COVID-19 Vaccination: An Endomyocardial Biopsy-
Proven Case Series. International Journal of Molecular Sciences 2022, Vol. 23, Page
6940 2022, 23 (13), 6940. https://doi.org/10.3390/IJMS23136940.
(17) Khan, S.; Shafiei, M. S.; Longoria, C.; Schoggins, J. W.; Savani, R. C.; Zaki, H. SARS-CoV-2
Spike Protein Induces Inflammation via TLR2-Dependent Activation of the NF-ΚB
Pathway. Elife 2021, 10, 68563. https://doi.org/10.7554/ELIFE.68563.
(18) Kulasinghe, A.; Liu, N.; Tan, C. W.; Monkman, J.; Sinclair, J. E.; Bhuva, D. D.; Godbolt, D.;
Pan, L.; Nam, A.; Sadeghirad, H.; Sato, K.; Bassi, G. L.; O’Byrne, K.; Hartmann, C.; dos
Santos Miggiolaro, A. F. R.; Marques, G. L.; Moura, L. Z.; Richard, D.; Adams, M.; de
Noronha, L.; Baena, C. P.; Suen, J. Y.; Arora, R.; Belz, G. T.; Short, K. R.; Davis, M. J.;
Guimaraes, F. S. F.; Fraser, J. F. Transcriptomic Profiling of Cardiac Tissues from SARS-
CoV-2 Patients Identifies DNA Damage. Immunology 2023, 168 (3), 403–419.
https://doi.org/10.1111/IMM.13577.
(19) Clough, E.; Inigo, J.; Chandra, D.; Chaves, L.; Reynolds, J. L.; Aalinkeel, R.; Schwartz, S.
A.; Khmaladze, A.; Mahajan, S. D. Mitochondrial Dynamics in SARS-COV2 Spike Protein
Treated Human Microglia: Implications for Neuro-COVID. Journal of Neuroimmune
Pharmacology 2021, 16 (4), 770. https://doi.org/10.1007/S11481-021-10015-6.
(20) Sheinin, M.; Jeong, B.; Paidi, R. K.; Pahan, K. Regression of Lung Cancer in Mice by
Intranasal Administration of SARS-CoV-2 Spike S1. Cancers (Basel) 2022, 14 (22), 5648.
https://doi.org/10.3390/CANCERS14225648/S1.
(21) Pfizer and BioNTech’s Vaccine Was Designed in Hours Over a Single Day.
https://www.businessinsider.com/pfizer-biontech-vaccine-designed-in-hours-one-
weekend-2020-12 (accessed 2023-04-04).
(22) Walsh, K. A.; Jordan, K.; Clyne, B.; Rohde, D.; Drummond, L.; Byrne, P.; Ahern, S.; Carty,
P. G.; O’Brien, K. K.; O’Murchu, E.; O’Neill, M.; Smith, S. M.; Ryan, M.; Harrington, P.
SARS-CoV-2 Detection, Viral Load and Infectivity over the Course of an Infection. J
Infect 2020, 81 (3), 357. https://doi.org/10.1016/J.JINF.2020.06.067.
(23) Seneff, S.; Nigh, G. Worse Than the Disease? Reviewing Some Possible Unintended
Consequences of the MRNA Vaccines Against COVID-19. International Journal of
Vaccine Theory, Practice, and Research 2021, 2 (1).
https://doi.org/10.56098/ijvtpr.v2i1.
(24) Altman, P. M.; Mitchell, L.; Faicd, M. The Time of Covid; 2022.
(25) Fraiman, J.; Erviti, J.; Jones, M.; Greenland, S.; Whelan, P.; Kaplan, R. M.; Doshi, P.
Serious Adverse Events of Special Interest Following MRNA COVID-19 Vaccination in
Randomized Trials in Adults. Vaccine 2022, 40 (40), 5798–5805.
https://doi.org/10.1016/J.VACCINE.2022.08.036.
(26) Skidmore, M. The Role of Social Circle COVID-19 Illness and Vaccination Experiences in
COVID-19 Vaccination Decisions: An Online Survey of the United States Population.
BMC Infect Dis 2023, 23 (1), 1–13.
https://doi.org/10.1186/S12879-023-07998-3/TABLES/4.
(27) Aarstad, J.; Kvitastein, O. A. Is There a Link between the 2021 COVID-19 Vaccination
Uptake in Europe and 2022 Excess All-Cause Mortality? 2023.
https://doi.org/10.20944/PREPRINTS202302.0350.V1.
(28) Coronavirus: anti-vaxxers seek to discredit Pfizer’s vaccine | Coronavirus | The
Guardian. https://www.theguardian.com/world/2020/nov/10/coronavirus-anti-
vaxxers-seek-to-discredit-pfizers-vaccine (accessed 2023-04-04).
(29) Over 100 million Americans may have seriously damaged their Heart due to Covid
Vaccination according to Expert Doctor – The Expose.
https://expose-news.com/2023/04/03/100m-americans-heart-disease-covid-
vaccination/ (accessed 2023-04-04).
(30) Planès, R.; Bert, J. B.; Tairi, S.; Benmohamed, L.; Bahraoui, E. SARS-CoV-2 Envelope (E)
Protein Binds and Activates TLR2 Pathway: A Novel Molecular Target for COVID-19
Interventions. Viruses 2022, 14 (5). https://doi.org/10.3390/V14050999.
(31) Jörrißen, P.; Schütz, P.; Weiand, M.; Vollenberg, R.; Schrempf, I. M.; Ochs, K.; Frömmel,
C.; Tepasse, P. R.; Schmidt, H.; Zibert, A. Antibody Response to SARS-CoV-2 Membrane
Protein in Patients of the Acute and Convalescent Phase of COVID-19. Front Immunol
2021, 12, 679841. https://doi.org/10.3389/FIMMU.2021.679841/BIBTEX.
(32) Grifoni, A.; Weiskopf, D.; Ramirez, S. I.; Mateus, J.; Dan, J. M.; Moderbacher, C. R.;
Rawlings, S. A.; Sutherland, A.; Premkumar, L.; Jadi, R. S.; Marrama, D.; de Silva, A. M.;
Frazier, A.; Carlin, A. F.; Greenbaum, J. A.; Peters, B.; Krammer, F.; Smith, D. M.; Crotty,
S.; Sette, A. Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans with
COVID-19 Disease and Unexposed Individuals. Cell 2020, 181 (7), 1489-1501.e15.
https://doi.org/10.1016/J.CELL.2020.05.015.
(33) Lu, J.; Lu, G.; Tan, S.; Xia, J.; Xiong, H.; Yu, X.; Qi, Q.; Yu, X.; Li, L.; Yu, H.; Xia, N.; Zhang,
T.; Xu, Y.; Lin, J. A COVID-19 MRNA Vaccine Encoding SARS-CoV-2 Virus-like Particles
Induces a Strong Antiviral-like Immune Response in Mice. Cell Research 2020 30:10
2020, 30 (10), 936–939. https://doi.org/10.1038/s41422-020-00392-7.
(34) Ma, X.; Zou, F.; Yu, F.; Li, R.; Yuan, Y.; Zhang, Y.; Zhang, X.; Deng, J.; Chen, T.; Song, Z.;
Qiao, Y.; Zhan, Y.; Liu, J.; Zhang, J.; Zhang, X.; Peng, Z.; Li, Y.; Lin, Y.; Liang, L.; Wang, G.;
Chen, Y.; Chen, Q.; Pan, T.; He, X.; Zhang, H. Nanoparticle Vaccines Based on the
Receptor Binding Domain (RBD) and Heptad Repeat (HR) of SARS-CoV-2 Elicit Robust
Protective Immune Responses. Immunity 2020, 53 (6), 1315-1330.e9.
https://doi.org/10.1016/J.IMMUNI.2020.11.015.
(35) Chen, K.; Cerutti, A. Vaccination Strategies to Promote Mucosal Antibody Responses.
Immunity 2010, 33 (4), 479–491. https://doi.org/10.1016/J.IMMUNI.2010.09.013.