A recent preprint by a Harvard researcher Kizzmekia Corbett & her team discusses the vaccine effectiveness one year later based on trials on non-human primates. It's been noted from "Breakthrough Infections" that Moderna outperforms Pfizer, even both these use the same mRNA technology.
Usually the correct approach is to perform a "Challenge trial" to ascertain the long term efficacy where the vaccinated individual is tested with the real pathogen itself. But with humans this cannot be done, due to ethical reasons, and hence performed using primates, in this case with Rhesus Macques. These primates share our genes to about 93% and are considered to be very good models to predict the outcomes on humans. So this team used these primates to test the vaccine efficacy.
The monkeys were injected with two doses of Spikevax (Moderna) vaccine, four weeks apart and then monitored by taking blood samples at different time intervals over the next year. At the 49th week they were "Challenged" with the Delta variant and further blood samples were taken.
These blood samples were used to test & analyze the ability of IgG antibodies contained to bind the RBD (receptor-binding domains) of three different viruses:
The blood resident IgG provides a major part of the immunity. These IgG levels were highest at 6 weeks after vaccination for all three viruses; they then declined rapidly between 6 weeks and 24 weeks, and more slowly between 24 weeks and 48 weeks. Most IgG detected at 6 weeks bound ancestral virus, with 5.4-fold and 8-fold fewer IgG molecules binding the delta and beta variants, respectively. However, when delta and beta variant-specific IgG antibodies were tested for their ability to block binding between SARS-CoV-2 and its cognate ACE2 receptor, they inhibited almost 100% of binding of both delta and beta variant viruses, suggesting that the antibodies were still functional in preventing infection, in spite of their diminished quantity.
After this they tested the nasal swabs and lung wash samples for Delta binding IgG & IgA antibodies. IgA antibodies dominantly present in mucosal surfaces and fluids. IgG behaviour was quite similar to the blood IgG as described above.
IgG levels in the nose was increasing till week 25, and remained stable through week 42. IgA levels in the lungs were highest at week 6 and decreased to unvaccinated levels by week 24. But IgA levels in the nose were similar to those in unvaccinated animals at all time points.
This difference between the lung & the nose, could explain why Covid vaccines are effective in preventing severe disease than preventing the infection itself.
Also Rapid and sustained protection in upper and lower airways may eventually require a boost.
The most interesting observation in the study relates to whether vaccinated individuals who become infected replicate and transmit virus to others. Analysis of lung wash samples for T cells specific for the SARS-CoV-2 N protein, which is not encoded in the Moderna vaccine, was only found the cells in unvaccinated animals.
This shows that after one year of vaccination, immunized animals did not replicate specific T cells for Covid N protein possibly because the virus was cleared out quickly.
PS: There are many other details in the preprint, available using this link.... https://www.biorxiv.org/content/10.1101/2021.10.23.465542v1.full.pdf
Dr Kizzmekia S Corbett is an US Immunologist who played a central part in developing the Moderna Vaccine. In February 2021, Corbett was highlighted in the Time's "Time100 Next" list under the category of Innovators.
Usually the correct approach is to perform a "Challenge trial" to ascertain the long term efficacy where the vaccinated individual is tested with the real pathogen itself. But with humans this cannot be done, due to ethical reasons, and hence performed using primates, in this case with Rhesus Macques. These primates share our genes to about 93% and are considered to be very good models to predict the outcomes on humans. So this team used these primates to test the vaccine efficacy.
The monkeys were injected with two doses of Spikevax (Moderna) vaccine, four weeks apart and then monitored by taking blood samples at different time intervals over the next year. At the 49th week they were "Challenged" with the Delta variant and further blood samples were taken.
These blood samples were used to test & analyze the ability of IgG antibodies contained to bind the RBD (receptor-binding domains) of three different viruses:
- “Ancestral” SARS-CoV-2, which had the exact spike protein antigen encoded in the vaccine.
- The Delta variant.
- The Beta variant.
The blood resident IgG provides a major part of the immunity. These IgG levels were highest at 6 weeks after vaccination for all three viruses; they then declined rapidly between 6 weeks and 24 weeks, and more slowly between 24 weeks and 48 weeks. Most IgG detected at 6 weeks bound ancestral virus, with 5.4-fold and 8-fold fewer IgG molecules binding the delta and beta variants, respectively. However, when delta and beta variant-specific IgG antibodies were tested for their ability to block binding between SARS-CoV-2 and its cognate ACE2 receptor, they inhibited almost 100% of binding of both delta and beta variant viruses, suggesting that the antibodies were still functional in preventing infection, in spite of their diminished quantity.
After this they tested the nasal swabs and lung wash samples for Delta binding IgG & IgA antibodies. IgA antibodies dominantly present in mucosal surfaces and fluids. IgG behaviour was quite similar to the blood IgG as described above.
IgG levels in the nose was increasing till week 25, and remained stable through week 42. IgA levels in the lungs were highest at week 6 and decreased to unvaccinated levels by week 24. But IgA levels in the nose were similar to those in unvaccinated animals at all time points.
This difference between the lung & the nose, could explain why Covid vaccines are effective in preventing severe disease than preventing the infection itself.
Also Rapid and sustained protection in upper and lower airways may eventually require a boost.
The most interesting observation in the study relates to whether vaccinated individuals who become infected replicate and transmit virus to others. Analysis of lung wash samples for T cells specific for the SARS-CoV-2 N protein, which is not encoded in the Moderna vaccine, was only found the cells in unvaccinated animals.
This shows that after one year of vaccination, immunized animals did not replicate specific T cells for Covid N protein possibly because the virus was cleared out quickly.
PS: There are many other details in the preprint, available using this link.... https://www.biorxiv.org/content/10.1101/2021.10.23.465542v1.full.pdf
Dr Kizzmekia S Corbett is an US Immunologist who played a central part in developing the Moderna Vaccine. In February 2021, Corbett was highlighted in the Time's "Time100 Next" list under the category of Innovators.
