July28  Unitedkingdom  2021 

*WearMask,KeepSanitizeYourHands*

Abstract Volume: 2 Issue: 4 ISSN:

Vaccine Efficacy on SARS-CoV-2 (COVID-19) Variants

Attapon Cheepsattayakorn1,2*, Ruangrong Cheepsattayakorn3, Porntep Siriwanarangsun1
 

1Faculty of Medicine, Western University, Pathumtani Province, Thailand

210th Zonal Tuberculosis and Chest Disease Center, Chiang Mai, Thailand

3Department of Pathology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand

 

*Corresponding Author: Attapon Cheepsattayakorn, 10th Zonal Tuberculosis and Chest Disease Center, 143 Sridornchai Road Changklan Muang Chiang Mai 50100 Thailand.


Received Date:  March 25, 2021

Publication Date: April 01, 2021


Abstract

The objectives of the study are to identify  current available  COVID-19  vaccines against  SARS-CoV-2 (COVID-19)  variants  of concern  and  their adverse  events.  A comprehensive  search  was carried  out  in mainstream  bibliographic  databases or  Medical  Subject Headings, including  ScienceDirect, PubMed, Scopus, and  ISI  Web of  Science.  The search was  applied to  the articles that were  published between  2020  and early  2021.    With strict literature  search and  screening  processes, it yielded  12  articles (2020 =  2; and early  2021  = 10  articles)  from 400  articles  of the initial  literature  database (2020-early  2021). The  WHO  recommendations  on COVID19  vaccines  in the  context  of SARS-CoV-2 (COVID-19)  variants  contribute to  the  plans of  the  next steps  on  COVID-19 vaccine  production, such  as Pfizer  and  BioNTech announced  on  February 25, 2021, that  they had  started  evaluating the  safety  and immunogenicity  of a  third dose  of  their vaccine  to  observe whether  it  would boost  immunity  to SARS-CoV-2 (C)OVID-19)  variants, particularly  B.1.351;Moderna announced on February 24, 2021 that it had shipped a booster vaccine candidate based on B.1.351 to NIAID for a phase 1 trial; and Novavax, whose the first-generation vaccine has not been authorized yet in the United States, announced on January 28, 2021 that it was working on developing a booster, a combination bivalent vaccine, or both to protect against SARS-CoV-2 (COVID-19) variants. From experience with avian coronavirus, vaccines against one variant will protect against similar variants, but not always against highly divergent variants. It is hard to predict long terms risk of immune escape. In long term, multivalent vaccines that include the viral nucleoprotein might be more robust. As SARS-CoV-2 (COVID-19) variants are too divergent, similar to flu vaccines, COVID-19 vaccines will be changed. In conclusion, rapid identification and characterization of variants of concern by the national and global surveillance will provide much more proactive. More challenging will be deciding when and how to deploy COVID-19 vaccines 2.0. Modifying COVID-19 vaccines would probably be the most straightforward step in involving SARS-CoV-2 (COVID-19) variants.

Keywords: COVID-19, SARS-CoV-2, Variants, Vaccines, Efficacy.

Abbreviations: COVID-19: Coronavirus Disease 2019, EUA: Emergency Use Authorization, hACE: human Anti-Converting Enzyme, PHEIC: Public Health Emergency of International Concern, SARS-CoV-2: Severe- Acute-Respiratory- Syndrome Coronavirus type 2, UK: United Kingdom, US CDC: United States Centers for Disease Control and Prevention.

Vaccine Efficacy on SARS-CoV-2 (COVID-19) Variants

Introduction

The first three COVID-19 vaccines with expressing spike Protein and a progressing national rollout has authorization of emergency use in the United Kingdom (UK) and demonstrated protection against COVID-19 (1,3) and decreased transmission after vaccination in the preliminary report (4). Challen et al indicated that B.1.1.7 variant might be related to increased mortality that supplements to the central questions of the ability of an old version of the spike the glycoprotein of SARS-CoV-2 (COVID-19) to produce protective antibodies against newer emerging variants (5). The current variants of concern, lineages B.1.351, B.1.1.7, and P1 affect the function of the spike protein and other SARS-CoV-2 proteins and can alter interaction with hACE2 (6).

 

Objectives of The Study

The objectives of the study are to identify current available COVID-19 vaccines against SARS-CoV-2(COVID-19) variants of concern and their adverse events.

 

Methods of The Study

A comprehensive search was carried out in mainstream bibliographic databases or Medical Subject Headings, including ScienceDirect, PubMed, Scopus, and ISI Web of Science. The search was applied to the articles that were published between 2020 and early 2021. Our first involved performing searches of article abstract/keywords/title using strings of [(“SARS-CoV-2” or “COVID-19”, “Vaccines”, “Variants” or “Variant”, “Vaccine Efficacy”, and “Vaccine Adverse Events”)]. After a first approach of search, published articles focusing on SARS-CoV-2 or COVID-19 vaccines were retained and the information on vaccine efficacy and vaccine adverse events were extracted for having a crude knowledge involving their themes.  Another round of publication search was conducted for adding the missing published articles that were not identified by the first round. 

 

All key words combinations from SARS-CoV-2, COVID-19, Variants, Vaccine Efficacy, Vaccine Adverse Events to bind the population of cases under consideration.  Search string for disease groups include [ “SARS-CoV-2” or “COVID-19” or “Variants” “Vaccine Efficacy” or “Vaccine Adverse Events”].  The  initial  literature databases  were  further manually  screened  with the  following  rules : 1)non-SARS-CoV-2, non-COVID-19, non-SARS-CoV-2 (COVID-19)  variants-related  articles were  excluded; 2) articles  that did  not  report SARS-CoV-2  or  COVID-19 related  to  vaccine efficacy  and  vaccine adverse  events  were not  considered, such  as commentary  articles, or  editorial; 3) non-peer-reviewed articles  were  not considered  to  be of  a  scholarly trustworthy  validity; and  4) duplicated and  non-English  articles were removed.  The articles were carefully selected to guarantee the literature quality, which is a trade-off for quantity. 

 

Results

With strict literature search and screening processes, it yielded 12 articles (2020 = 2; and early 2021 =10 articles) from 400 articles of initial literature database (2020-early 2021). Needed article information was extracted from each article by : 1) direct information including journal, (research article, review article, meeting abstract, conference abstract, correspondence, author index, editorial board meeting abstract, discussion), book chapter, title, authors, abstract, full text documents of candidate studies, publishing year; 2) study period; 3) research (study) method used;; and 4) the conclusions made about  the SARS-CoV-2 (COVID-19) vaccine efficacy and vaccine adverse events on humans infected with SARS-CoV-2 (COVID-19) variants.

 

Classifications and Definitions of SARS-CoV-2 (COVID-19) Variants

Due to the recent emergence of variants of SARS-CoV-2 (COVID-19), this powerfully contributes to the adapting scientific response to remain effective against the very naturally mutated viruses (7). The United States Centre for Disease Control and Prevention (US CDC) classifies the SARS-CoV-2 (COVID-19) variants as the following (8):   

 

1. A variant of Interest   These variants are currently interesting in the United States.  These variants  are  (1.1) B.1.526 (First  detected in  New  York, November  2020, with potential  reduction  in neutralization  by  monoclonal antibody  treatments  and potential reduction  in neutralization  by  convalescent and  post-vaccination sera), 1.2) B.1.525 (First  detected in  New  York, December 2020, with potential  reduction  in neutralization  by  monoclonal antibody  treatments  and potential  reduction  in neutralization  by convalescent and  post-vaccination  sera), and 1.3) P.2 (First detected  in Brazil, April  2020, with  potential reduction  in  neutralization  by monoclonal  antibody  treatments and  potential  reduction in  neutralization  by convalescent  and  post-vaccination  sera)

 

2. Variants  of Concern These  variants are  2.1) B.1.1.7 (First detected in  the  United Kingdom, with  approximately  50 % increased  transmissibility likely  increased  severity based  on  hospital admissions  and  case fatality  rates, minimal  impact on  neutralization  by Emergency  Use  Authorization (EUA) monoclonal antibody  treatments, and  minimal impact  on  neutralization  by convalescent  and  post-vaccination  sera), 2.2)P.1 (First  detected in  Japan  or Brazil, with  moderate  impact on  neutralization  by  EUA  monoclonal antibody  treatments, and  reduced neutralization  by  convalescent and  post-vaccination sera), 2.3) B.1.351 (First  detected in  South  Africa, with approximately  50 %  increased transmissibility, moderate impact  on  neutralization  by  EUA  monoclonal antibody  treatments, and moderate reduction  on  neutralization  by convalescent  and  postvaccination  sera), 2.4) B.1.427 (First  detected in  California, with  approximately 20 %  increased  transmissibility, significant impact on  neutralization  by some, but  not  all, EUA treatments and  moderate  reduction in  neutralization  using convalescent and  post-vaccination  sera), and  2.5) B.1.429 (First  detected  in California, with  approximately  20 % increased  transmissibility, significant  impact  on neutralization  by  some, but not  all, EUA treatments, and  moderate reduction  in  neutralization  using convalescent  and  post-vaccination  sera)  

3. Variant of High Consequence This variant has clear evidence that medical countermeasure (MCMS) or prevention measures have significantly decreased effectiveness that are associated with previously circulating variants. The possible attributes that can impact MCMS have demonstrated the failure of diagnostics, evidence to indicate a significant reduction in vaccine effectiveness, a disproportionately high number of vaccines breakthrough cases, very low vaccine-induced protection against severe disease, significantly decreased susceptibility to multiple EUA or approved treatments, and more severe clinical disease and increased hospital admissions. This variant would require public health officials to announce a Public Health Emergency of International Concern (PHEIC).  

 

Vaccine Efficacy on SARS-CoV-2 (COVID-19) Variants

Recently, in  early March  2021, a  study demonstrated  the  efficacy of  various  COVID-19 vaccines  produced  by many  manufactures  in  symptomatic  SARS-CoV-2 (COVID-19)  patients and  patients  infected with  SARS-CoV-2 (COVID-19)  variants as  the  following manufactures (vaccine  name), used technology,doses, efficacy  against symptomatic  disease, and efficacy against  variants (B.1.1.7 (first  detected  in the  United  Kingdom) and  B.1.351 (first  detected in  South  Africa)) : 1) Pfizer and  BioNTech (Comirnaty), mRNA, 2  doses, 95 %, unknown, and unknown; 2) Oxford  and AstraZeneca (AZD1222), viral vector, 2 doses, 82.4 % (12  weeks  between  doses), 74.6 %, to  be confirmed (unconfirmed reports  as  low as  10 %); 3) Moderna and the  National  Institute of  Health (NIH) (mRNA-1273), mRNA, 2 doses, 94.5 %, unknown (but  reports of  reduction  in neutralizing antibodies), unknown; 4) Gamaleya (Sputnik V), viral  vector, 2 doses, 91.6 %, unknown, unknown; 5) CanSinoBio (Convidecia),viral  vector, 1  dose, 65.7 %, unknown, unknown; 6)Novavax (NVX-CoV2373), protein, 2  doses, 95.6 %, 85.6 %, 60%; 7) John &  Johnson (Ad26.COV2.S), viral  vector, 1  dose, 72%, unknown, 57 %; 7) Sinopharm (BBIBP-CorV), inactivated virus, 2  doses, 79.34 %, unknown, unknown (but  reports of weekend  effect); 8) Sinovac (CoronaVac), inactivated  virus, 2 doses, 50.4 %, unknown, unknown; and  8) Bharat Biotech(Covaxin), inactivated virus, 2  doses, unknown, unknown, unknown; respectively (9)

 

Discussion

SARS-CoV-2 (COVID-19) variants of concern might be related to changes in both morbidity and mortality.  Suppression of the host immune response, altered viral transmission dynamics, or higher viral loads in COVID-19-infected persons might worsen the clinical outcomes.  The serious adverse events from AZD1222 occurred in 168 patients, 79 in the vaccine group, and 89 in the control group (9).  Two cases demonstrated transverse myelitis that later determined to be unlikely to be associated (9), whereas, there are unknown serious adverse events from CoronaVac in phase III trials (9).  More serious adverse events were reported in the control group than in the vaccine group (9).

 

Recently, the World Health Organization (WHO) stated that in the context without SARS-CoV-2 (COVID-19) variants, particularly B.1.351, the Oxford/AstraZeneca vaccine offers protection against severe COVID-19, COVID-19-related hospitalization, and COVID-19-related death (7).  Interestingly, the difference in the vaccine efficacy of the Ad26COV2.S COVID-19 vaccine was demonstrated in the United States and South Africa (72 % vs 57 %) (10). The South Africa trials demonstrated lower vaccine efficacy compared with trials in other countries where the B.1.351 variant was not dominant (11), whereas a recent study demonstrated that a two-dose regimen of the ChAdOx1 nCoV vaccine did not protect against mild-to-moderate B.1.351 COVID-19 variant (12).  Current COVID-19 vaccines are based on the SARS-CoV-2 spike protein, whereas the SARS-CoV-2 (COVID-19) variants contain mutations in the spike protein that contributes to spurring vaccine efficacy concerns (11).

 

The  WHO recommends on the effectiveness of  COVID-19 vaccines in the context of  SARS-CoV-2 (COVID-19)  variants that 1) The manufacturers must be prepared to adjust to the  SARS-CoV-2 (COVID-19)  viral evolution, 2) Trials must be designed and maintained to allow any changes in efficacy to be assessed, 3) Enhanced genomic surveillance must be backed by rapid haring of genetic and meta-data to allow for global coordination and response, 4) Priority should be given to vaccinating high-risk groups everywhere, 5) Governments and donors, as well as development banks, should further support  COVAX, and 6) The existing mechanism for tracking and evaluating  COVID-19  variants that may affect vaccine composition must be enhanced (7).

 

The WHO recommendations on  COVID-19 vaccines in the context of  SARS-CoV-2 (COVID-19)  variants contribute to the plans of the next step on COVID-19  vaccine production, such as Pfizer and  BioNTech announced on  February 25, 2021, that they had started evaluating the safety and immunogenicity of a third dose of their vaccine to observe whether it would boost immunity to SARS-CoV-2 (C)OVID-19)  variants, particularly B.1.351; Moderna announced on  February  24, 2021, that it had shipped a  booster vaccine candidate based on  B.1.351  to NIAID for a phase  1  trial; and Novavax, whose first-generation vaccine has not been authorized yet in the United  States, announced on January  28, 2021, that it was working on developing a booster, a combination bivalent vaccine, or both to protect against  SARS-CoV-2 (COVID-19)  variants (11).

 

From experience with avian coronavirus, vaccines against one variant will protect against similar variants, but not always against highly divergent variants.  It is hard to predict log terms of the risk of immune escape.  In long term, multivalent vaccines that include the viral nucleoprotein might be more robust. As SARS-CoV-2 (COVID-19) variants are too divergent, similarto flu vaccines, COVID-19 vaccines will be changed.  

 

Conclusion 

Rapid identification and characterization of variants of concern by the national and global surveillance will provide much more proactive.  More challenging will be deciding when and how to deploy COVID-19 vaccines 2.0.  Modifying COVID-19 vaccines would probably be the most straightforward step in involving SARS-CoV-2 (COVID-19) variants.

 

References

1.Voysey M, Clemens SAC, Madhi SA, et al.  “Oxford COVID-19 Vaccine Trial Group”.  Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomized controlled trials in Brazil, South Africa, and the UK.  Lancet 2021; 397: 99-111.

2. Baden LR, El Sahly HM, Essink B, et al.  “COVE Study Group”.  Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine.  N Engl J Med 2021; 384: 403-416.  DOI: 10.1056/NEJMoa2035389 pmid: 33378609

3. Polack FP, Thomas SJ, Kitchin N, et al.  “C4591001 Clinical Trial Group”.  Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine.  N Engl J Med 2020; 383: 2603-2615.

4. Levine-Tiefenbrun M, Yelin I, Katz R, et al.  “Decreased SARS-CoV-2 viral load following vaccination”.  medRxiv 2021: 2021.02.06.21251283 

DOI: 10.1101/2021.02.06.21251283  

5. Challen R, Brooks-Pollock E, Read JM, Dyson L, Tsaneva-Atanasova K, Danon L.  “Risk of mortality in patients infected with SARS-CoV-2 variant of concern 202012/1: matched cohort study”.  BMJ  2021; 372: n579.  DOI: 10.1136/bmj. N 579 pmid: 33687922.  

6. Yi C, Sun X, Ye J, et al. “Key residuals of the receptor binding motif in the spike protein of SARS-CoV-2 that interact with ACE2 and neutralizing antibodies”.  Cell Mol Immunol 2020; 17: 621-630. 

DOI: 10.1038/s41423-020-0458-z pmid: 32415260.

7. “World Health Organization”. COVAX Statement on New Variants of SARS-CoV-2.  Printed Online: February 8, 2021.  Available at: www.who.int>News>item (accessed on March 20, 2021). 

8. “United States Center for Disease Control andPrevention”.  SARS-CoV-2 variants classifications and definitions.  Updated on March 16, 2021.  Available at: www.cdc.gov>variant-surveillance>variants-info (accessed on March 20, 2021).

9. “Mahase E”.  COVID-19: where are we on vaccines and variants?  BMJ  2021; 372: n597.  Published Online: March 2, 2021.  DOI: http://dx.doi.org/10.1136/bmj.n597 

10. Cohen J.  “One-dose of COVID-19 vaccine offers solid protection against severe disease”.  Science 2021.  Published Online: January 29, 2021.  DOI: https://doi.org/10.1126/science.abg7115 

11. Rubin R.  “COVID-19 vaccines vs variants-determining how much immunity is enough”.  JAMA, Medical News & Perspectives. Published Online: March 17, 2021.11 pages.  DOI: 10.1001/jama.2021.3370 Available at: www.jamanetwork.com>journals>jama>full-article (accessed on March 20, 2021).

12. Madhi SA, Baillie CL, Cutland M, Voysey AL, Koen L, Fairlie SD, et al.  “Efficacy of the ChAdOx1 nCoV-19 COVID-19 Vaccine against the B.1.351 Variants”.  N Engl J Med 2021.  14 pages.  Published Online: March 16, 2021.  DOI: 10.1056/NEJMoa2102214

 

Volume 2 Issue 4 April 2021

©All rights reserved by Attapon Cheepsattayakorn