A team of researchers at the University of Texas has reported that modified vaccines could beat the pandemic.
They first created four chimeric SARS-CoV-2 viruses, each bearing a distinct variant spike gene from the alpha (B.1.1.7), beta (B.1.351), gamma (P.1; Brazil), or epsilon (B.1.429; California] lineages in the backbone of an early wild-type (WT) virus. These four variants were selected based on their high prevalence at the onset of the project. Each variant spike contained a distinct set of mutations. An additional substitution E484K was added to the original Alpha variant (Alpha+E484K) as this mutation occurred in many clinical isolates. The spike genes from all recombinant viruses were sequenced to ensure no aberrant mutations.
To test the immunogenicity of each variant hamsters were intranasally immunized hamsters with 10^6 PFU (plaque-forming units) of recombinant WT or the variant-spike virus.
Serum samples taken on days 14, 28, and 45 post-immunization were tested for neutralizing titers against both homologous and heterologous variant-spike viruses, including the currently prevalent delta-spike virus.
They found that, each variant spike elicited faster and more potent neutralizing activity against their homologous SARS-CoV-2 variant than they did against heterologous variants, including the delta variant. On days 14, 28, and 45 post-immunization, the differences in neutralizing titers generated against homologous and heterologous variants were as large as 62-, 15-, 9.7-fold, respectively.
Then to evaluate cross protection, they selected the variant viruses that exhibited the lowest neutralizing titers in each immunized group and challenged the animals on day 49 post-immunization.
Specifically, animals immunized with the WT, alpha, beta, gamma, or epsilon spike were challenged with 10^4 PFU of beta, delta, epsilon, epsilon, and gamma-spike SARS-CoV-2, respectively.
Compared with control mice that received phosphate-buffered saline, all variant spike-immunized hamsters exhibited significant protection following the challenge. Viral loads were 82- to 10,112-fold lower in nasal washes, 955- to 120,000-fold lower in the animals’ tracheas and 57,000- to 490,000-fold lower in the lungs.
The closing summary of their paper states "Increasing global immunization with the currently available safe and effective vaccines, together with boosters when needed, is the strategy to end the COVID-19 pandemic. The design of the booster vaccines depends on whether the newly emerged variants can escape the immunity generated by the current vaccines or natural infections. Potential immune escape of any new variants should be closely monitored by laboratory studies and real-world breakthroughs in vaccinated and infected individuals."
Full pre-print is available on this link... https://doi.org/10.1101/2021.09.02.458740
They first created four chimeric SARS-CoV-2 viruses, each bearing a distinct variant spike gene from the alpha (B.1.1.7), beta (B.1.351), gamma (P.1; Brazil), or epsilon (B.1.429; California] lineages in the backbone of an early wild-type (WT) virus. These four variants were selected based on their high prevalence at the onset of the project. Each variant spike contained a distinct set of mutations. An additional substitution E484K was added to the original Alpha variant (Alpha+E484K) as this mutation occurred in many clinical isolates. The spike genes from all recombinant viruses were sequenced to ensure no aberrant mutations.
To test the immunogenicity of each variant hamsters were intranasally immunized hamsters with 10^6 PFU (plaque-forming units) of recombinant WT or the variant-spike virus.
Serum samples taken on days 14, 28, and 45 post-immunization were tested for neutralizing titers against both homologous and heterologous variant-spike viruses, including the currently prevalent delta-spike virus.
They found that, each variant spike elicited faster and more potent neutralizing activity against their homologous SARS-CoV-2 variant than they did against heterologous variants, including the delta variant. On days 14, 28, and 45 post-immunization, the differences in neutralizing titers generated against homologous and heterologous variants were as large as 62-, 15-, 9.7-fold, respectively.
Then to evaluate cross protection, they selected the variant viruses that exhibited the lowest neutralizing titers in each immunized group and challenged the animals on day 49 post-immunization.
Specifically, animals immunized with the WT, alpha, beta, gamma, or epsilon spike were challenged with 10^4 PFU of beta, delta, epsilon, epsilon, and gamma-spike SARS-CoV-2, respectively.
Compared with control mice that received phosphate-buffered saline, all variant spike-immunized hamsters exhibited significant protection following the challenge. Viral loads were 82- to 10,112-fold lower in nasal washes, 955- to 120,000-fold lower in the animals’ tracheas and 57,000- to 490,000-fold lower in the lungs.
The closing summary of their paper states "Increasing global immunization with the currently available safe and effective vaccines, together with boosters when needed, is the strategy to end the COVID-19 pandemic. The design of the booster vaccines depends on whether the newly emerged variants can escape the immunity generated by the current vaccines or natural infections. Potential immune escape of any new variants should be closely monitored by laboratory studies and real-world breakthroughs in vaccinated and infected individuals."
Full pre-print is available on this link... https://doi.org/10.1101/2021.09.02.458740
