Vaccine and Variants: 1stGeneration vaccine good enough for new COVID-19 Variants?

Vaccine and Variants: 1stGeneration vaccine good enough for new COVID-19 Variants?
May 3, 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have inflicted on approximately 150 million known cases of coronavirus disease 2019 (Covid-19) till date (1). Vaccines and antibody therapies have given us lot of hope to control this pandemic thus controlling the death. The current vaccine strategies are directed at the viral “spike protein or S gene”, but newer viral variants, particularly the S gene variants, weakens this strategy. Thus vaccine resistance (Vaccine Breakthrough Infections both asymptomatic and illness) has emerged a new challenge for our scientists and physicians.

Recently, New York City has seen a troubling increase in viral variants like B.1.1.7 (first identified in the United Kingdom in 26.2% of the cases) that accounted for more than 72% of new cases as of March 2021 and B.1.526 variant first identified in New York City (in 42.9%) (2). These challenges force us to continually increase testing and sequencing of the SARS-CoV-2 virus. This will help to understand the transmissibility, virulence, and ability of variants to evade current vaccines.

Currently, authorized and recommended vaccines are mainly of three types.

  • mRNA Vaccine. RNA sequence representingSARS-CoV-2 is injected. The body makes a copy of harmless proteins unique to the virus. Then body’s immune mechanism recognizes the new protein and build T-lymphocytes and B-lymphocytes against the protein. The immunity is then good enough to fight against the virus.

Examples – Pfizer-BioNTech, Moderna.

 Challenge– The new spike protein variants (S gene variants) have different protein structures as compared to the parent strain (Wuhan). Thus rendering the vaccine-generated immune response ineffective.

Laboratory Data on the messenger RNA (mRNA) vaccines’ efficacy against SARS-CoV-2 variants has been generated using genetically engineered versions of concerning variants and measuring neutralizing antibody titers. Research studies have shown these vaccines elicit lower levels of neutralizing antibody response against SARS-CoV-2 variants than against older common strains. Testing serum samples from individuals immunized with 2 doses of the Pfizer-BioNTech vaccine against recombinant viruses containing some or all of the spike protein mutations found in the B.1.351 variant, the Neutralizing antibody titer against B.1.351 was approximately two-thirds lower than that of USA-WA1/2020, an early SARS-CoV-2 isolate (3).

Advantage- The neutralizing antibody titer may be low but may provide protection against infection to some extent and severe complications. Modifying the RNA sequence, incorporating the mutant sequence while vaccine preparation is feasible. Thus the newer version of tailored made vaccine or cocktail can be easily manufactured and given a booster dose. But definitely requires regulatory clearance every time.

Conclusion-1stGenerationmRNA vaccine is not proven to be very effective for the newer variants. The real-world data is yet immature to make final recommendation. New booster dose incorporating the mutant sequence is currently being in early phase trials to circumvent these challenges.


  • Vector Vaccine. The technology used is likepiggy backing”SARS-CoV-2 genetic material (incomplete) into a replicating live attenuated virus (called as Viral vector e.g. Adenovirus), thus generating a new modified virus. This modified virus is given as vaccine, once inside our cells, the genetic material is released and copies of new proteins unique to the COVID-19 virus is generated. This prompts our bodies to build T-lymphocytes and B-lymphocytes against the new protein and protect against the viral infection.

Examples – Covishield (Oxford-AstraZeneca), Johnson & Johnson/ Janssen Vaccine


Challenge– The genetic material used for piggy back represent the early SARS-CoV-2 virus not the variants. Thus rendering the vaccine generated immune response ineffective for the variants.

Phase II trial withOxford-AstraZeneca vaccine in South Africa was not encouraging. The trial data suggest that the vaccine did not protect against mild to moderate COVID-19 caused by the B.1.351 variant(4).

Advantage- The genetic material used is large enough to represent the majority portion of the viral genetic make-up, thus covers more possibilities of generating polyclonal immune responses targeting multiple virus protein/peptide sequences. In Scotland, researchers showed that Oxford-AstraZeneca’s vaccine up to 94% effective compared to mRNA vaccine Pfizer-BioNTech’s vaccine up to 85% effective in preventing COVID-19–related hospitalizations 28 to 34 days after a single dose (5).

The neutralizing antibody titre may be low albeit the immunity generated is polyclonal covering larger sequences and may provide better protection against infection including severe complications.

Conclusion- 1st Generation Vector vaccine is yet to proven to be effective for the newer variants. The real world data is awaited.

Protein subunit vaccines. The vaccine is made up of protein/peptiderepresenting  SARS-CoV-2 virus. Once vaccinated, bodies recognize the protein as foreign and build T-lymphocytes and antibodies against it leading to generation of immunity against the virus. Example- Covaxin (Bharat Biotech International Ltd), Novavax

Challenge– The protein/peptide material used to represent the early SARS-CoV-2 virus not the variants. Thus rendering the vaccine-generated immune response incomplete for the variants.

 Advantage- This is the most established and proven method of vaccination like Seasonal influenza, Rabies, Polio, Pertussis, and Japanese encephalitis. Data suggest that NovavaxClinical Efficacy is Against both COVID-19 and Both UK and South Africa Variants. Strong efficacy has been observed in Phase 3 UK trial where over 50% of cases are attributed to the now-predominant UK variant and the remainder attributable to COVID-19 virus. Similarly, in Phase 2b South Africa trial, clinical efficacy has been demonstrated, with over 90% of sequenced cases attributable to prevalent South Africa escape variant (5).

Conclusion- 1st Generation Protein subunit vaccine has shown to be effective for the newer variants. More data including responses against other variants need close observation and data generation.

The current vaccine has proven to generate neutralization antibody leading to reduced hospitalization and complication rate. In addition, the lateral spread among the community has also reduced where a significant population has been vaccinated. Thus the current vaccination has proven to be efficacious to the original strain of SARS- CoV-2 and should be promoted and continued for mass immunization.

To conclude the aspect of vaccine efficacy and emerging new variants, we require a newer version/generation of vaccines. These newer generations may be given as booster doses in the future.

Posted in MolQ