Opinion

Following the spread of the different Viral Variants of COVID-19 [1-5] which seems unstoppable, perhaps a strategy could be implemented for the production of a DEFINITIVE vaccine capable of neutralizing the Virus despite the presence of variants. A few days ago I appreciated the good news that researchers published about the vaccine with the covid N protein in mice [6]. This confirms that multiple targets such as antigens allow to overcome the appearance of variants. Howewver, vaccination experiments on animals in the laboratory, as a preclinical model, are valid but it must be careful in extrapolating them to humans. The mice used are often of the same age and genetically “IMBRED”; that is, their immune system is not genetically polymorphic, they live in very controlled conditions and are often the same age. The human immune system, on the other hand, is different in that it is subject to many parameters and is regulated by multiple polymorphisms which, as is well known, induce considerable variability as is widely demonstrated in daily practice: in timing, in dose; in effectiveness; in duration etc. Starting from these considerations, to generate a Definitive Vaccine, a valid procedure could be the following: all Healed and Asymptomatic patients, after infection with the different viral variants, have generated antibodies, contained in their blood, against all the antigenic components of the WHOLE VIRUS, including the Spike protein which represents only the most attackable antigen but not the only one [7]. That is, antibodies directed towards the protein sequences of viral antigens which physiologically cannot be subject to mutations are present.

Moreover the pool of antibodies taken from cured and asymptomatic patients, after infection with all viral variants, can be also used as probe to identify phylogenetic common antigenic epitopes present in all coronaviruses in addition to the specific ones induced by single variants. The conserved epitopes [8,9] allow generating immunity that is not only cross-protective over coronaviruses but also relatively resistant to ongoing Covid evolution. In addition, this strategy could be applied to fight soon future pandemics by using the available first sera from haeled and asymptomatics patients. Synthetic peptides (small molecules of 25 Amino acids), which sequences reflect the selected epitopes, recognized by the pool of sera from selected patients, allows the possibility of producing large quantities of vaccine at relatively low cost and easy handling in the transport and storage chain and methods of administration like nasal spray, sublingual absorption as well as intramuscular.

Methods

Immunoaffinity Chromatography to purify synthetic peptides recognized by human antibodies. Synthetic peptides of 25 Amino Acids reflect the protein sequences of SPIKE, N and M antigens of Covid. The peptides retained in the column and then eluted after washing can be used as vaccine in preclinical models to test anti variants-Covid efficacy.

References

1. Hoffmann M, Arora P, Groß R, Seidel A, Hornich B F, et al. (2021) SARS-CoV-2 variants B.1.351 and P.1 escape from neutralizing antibodies. Cell 2021 184(9): 2384-2393.
2. Kidd M, Richter A, Best A, Cumley N, Mirza J, et al. (2021) S-Variant SARS-CoV-2 Lineage B1.1.7 is Associated with significantly higher viral load in Samples Tested by TaqPath Polymerase Chain Reaction. J Infect Dis 223(10): 1666-1670.
3. Leung K, Shum M H, Leung G M, Lam T T, Wu J T, et al. (2020) Early transmissibility assessment of the N501Y mutant strains of SARS-CoV-2 in the United Kingdom, October to November 2020. Euro Surveill 26(1): 2002106.
4. Mwenda M, Saasa N, Sinyange N, Busby G, Chipimo P J, et al. (2021) Detection of B.1.351 SARS-CoV-2 Variant Strain-Zambia, December 2020. MMWR Morb Mortal Wkly Rep 70(8): 280-282.
5. Da Silva Francisco R, Benites L F, Lamarca A P, de Almeida L G P, Hansen A W, et al. (2021) Pervasive transmission of E484K and emergence of VUI-NP13L with evidence of SARS-CoV-2 co-infection events by two different lineages in Rio Grande do Sul, Brazil. Virus Res 296: 198345.
6. Flavia Ferrantelli, Chiara Chiozzini, Francesco Manfredi, Patrizia Leone, Massimo Spada, et al. (2022) Strong SARS-CoV-2 N-Specific CD8+ T Immunity Induced by Engineered Extracellular Vesicles Associates with Protection from Lethal Infection in Mice. Viruses 14(2): 329.
7. Lianpan Dai, George F Gao (2021) Review: Viral targets for vaccines against COVID-19. Nat Rev Immunol 21(2): 73-82.
8. Qiu T, Mao T, Wang Y, Zhou M, Qiu J, et al. (2020) Identification of potential cross-protective epitope between a new type of coronavirus (2019-nCoV) and severe acute respiratory syndrome virus. J Genet Genom 47(2): 115-117.
9. Michela Murdocca, Gennaro Citro, Isabella Romeo, Antonio Lupia, Shane Miersch, et al. (2021) Peptide Platform as a Powerful Tool in the Fight against COVID-19. Viruses 13(8): 1667.

ABSTRACT

Following the spread of the different Viral Variants of COVID-19 [1-5] which seems unstoppable, perhaps a strategy could be implemented for the production of a DEFINITIVE vaccine capable of neutralizing the Virus despite the presence of variants. A few days ago I appreciated the good news that researchers published about the vaccine with the covid N protein in mice [6]. This confirms that multiple targets such as antigens allow to overcome the appearance of variants. Howewver, vaccination experiments on animals in the laboratory, as a preclinical model, are valid but it must be careful in extrapolating them to humans. The mice used are often of the same age and genetically “IMBRED”; that is, their immune system is not genetically polymorphic, they live in very controlled conditions and are often the same age. The human immune system, on the other hand, is different in that it is subject to many parameters and is regulated by multiple polymorphisms which, as is well known, induce considerable variability as is widely demonstrated in daily practice: in timing, in dose; in effectiveness; in duration etc. Starting from these considerations, to generate a Definitive Vaccine, a valid procedure could be the following: all Healed and Asymptomatic patients, after infection with the different viral variants, have generated antibodies, contained in their blood, against all the antigenic components of the WHOLE VIRUS, including the Spike protein which represents only the most attackable antigen but not the only one [7]. That is, antibodies directed towards the protein sequences of viral antigens which physiologically cannot be subject to mutations are present.