Principles Learned from the International Race to Develop a Safe and Effective COVID-19 Vaccine

Abstract

Vaccines against COVID-19 have the potential to protect people before they are exposed to the infective form of the virus. However, because of the involvement of pathogenic immune processes in many severe presentations of COVID-19, eliciting an immune response with a vaccine must strike a delicate balance to achieve viral clearance without also inducing immune-mediated harm. This Outlook synthesizes current laboratory findings to define which parts of the immune system help with recovery from and protection against the virus and which can lead to adverse outcomes. To inform our understanding, we analyze research about the immune mechanisms implicated in SARS-CoV, from the 2003 outbreak, and SARS-CoV-2, the virus causing COVID-19. The impact of how innate immunity, humoral immunity, and cell-mediated immunity play a role in a harmful versus helpful response is discussed, establishing principles to guide the development and evaluation of a safe but effective COVID-19 vaccine. The principles derived include (i) targeting the appropriate specificity and effector function of the humoral response, (ii) eliciting a T cell response, especially a cytotoxic T cell response, to achieve safe, yet effective, immune protection from COVID-19, and (iii) monitoring for the possibility of acute lung injury during SARS-CoV-2 infection post-vaccination in preclinical and clinical studies. These principles can not only guide efforts toward a safe and effective COVID-19 vaccine, but also the development of effective vaccines for viral pandemics to come.

A Comprehensive Review of the Global Efforts on COVID-19 Vaccine Development

“…The in situ synthesis of these foreign immunogens within the host cells effectively elicits both antibody production and T-cell induction, which are important parameters of protection as observed in convalescent COVID-19 patients. 48 − 51 In addition, nucleic acid vaccines can more easily be manufactured on a large scale.…”

“…Similar to viral vector vaccines, nucleic acid vaccines introduce genetic instructions (DNA or mRNA encoding disease-specific antigens) to host cells and utilize the host cells’ protein-making machinery to generate immunogens. The in situ synthesis of these foreign immunogens within the host cells effectively elicits both antibody production and T-cell induction, which are important parameters of protection as observed in convalescent COVID-19 patients. − In addition, nucleic acid vaccines can more easily be manufactured on a large scale.…”

COVID-2019: Una revisión de la nueva crisis pandémica

“…Está claro que el objetivo de obtener una vacuna contra el COVID-19 es proteger a las personas antes de que se expongan al virus y, en la búsqueda de alcanzar la eliminación viral, induciendo en la persona vacunada una respuesta inmune, se está produciendo un cambio en el equilibrio inmunológico de su organismo y, una vez superado este proceso, debe alcanzar de nuevo el equilibrio sin producir ningún daño. En este sentido, se han establecido una serie de principios que se deben cumplir para obtener una vacuna segura y efectiva contra el COVID-19 (Thames et al, 2020), los cuales toman en cuenta la importancia de la especificidad de los anticuerpos humorales y la respuesta de las células T (Chen & Wherry, 2020). Hasta el momento, las investigaciones publicadas sobre el MERS y SARS aportan infomación valiosa (Al-Kassmy et al, 2020), entre otras que el receptor clave es la enzima convertidora de angiotensina 2 humana (ACE2).…”

Identification of Potential Anti‐COVID‐19 Drug Leads from Medicinal Plants through Virtual High‐Throughput Screening

“…[1][2][3][4][5][6] Vaccines (and antibodies) target mainly Spike protein on the viral surface which is necessary for recognizing and binding to the human angiotensin-converting enzyme 2 (ACE2) receptor during viral entry. [5][6][7][8][9][10][11][12] The antiviral drugs target some key proteins involved in the viral replication machinery, such as the RNA-dependent RNA polymerase (RdRp) which synthesizes viral RNA and two conserved viral cysteine proteases, main protease (M pro ) and papain-like protease (PL pro ) which process the polyprotein chains translated from the viral RNA and cleave the chains into functional proteins that are required for viral replication, transcription, and assembly. [1,4,[10][11][12][13][14][15][16][17][18][19][20][21] It is important to note that since there are many mutation-prone residues in different targets -especially in the viral Spike protein -thus a successful vaccine or drug should be less sensitive to the variants and be effective against these mutations.…”