Coronavirus (29) Pre-existing immunity to adenovirus type 5 and type 26
In my last blog post, I mentioned that previous infection by a human adenovirus could decrease the efficacy of vaccines that use that adenovirus as a backbone. The best way to avoid using adenovirus vaccines that we may be immune to, is to use a viral vectored vaccine with a non-human adenovirus vector, like the AZD1222 by AstraZeneca and Oxford University, which uses chimpanzee adenovirus. Human populations around the world have a much lower level of pre-existing immunity to the chimpanzee adenovirus.
Alternatively, we can check our serum antibody levels to the adenovirus. However, as most of us are not virology or vaccine experts, we won’t know what is an acceptable level of neutralizing antibodies against the adenovirus used by the vaccine we are thinking of taking.
There were studies performed to check the pre-existing immunity to Adenovirus type 5 (Ad5) and Adenovirus type 26 (Ad26), the two common human adenoviruses used by the adenovirus vectored vaccines for COVID-19, in different populations, by testing the serum neutralizing antibodies to the two adenoviruses. I have put together the data from two of the studies into the table below.1-2 Looking at this data may give us an idea of which type of vaccine to use, if we were given a choice.
As we can see from the table, Ad5 infection is generally more common than Ad26 in all the nations studied. The infection rate of Ad5 is at least 50% higher than that of Ad26. Moreover, people in the developing world seems to have higher adenovirus infection rate. Detailed data (not shown in this table) from the results of the multinational study1 also showed a much higher proportion of people with high level of blood antibody against Ad5 in the high Ad5 prevalence areas, in contrast to markedly fewer individuals in these regions demonstrating a high level of blood antibody to Ad26.1 Data also showed that the median level of blood antibody to Ad26 in the 4381 international test participants was approximately 10-fold lower than the median level of blood antibody to Ad5.
The data from the studies did not include populations from all countries around the world, and the studies were done at least 7 years ago. I cannot find any more up-to-date data on studies comparing the prevalence of Ad5 and Ad26 infections. However, the above data gives us a general idea that people in developing countries should try to avoid using Ad5 vectored vaccines. If we were given a chance to choose from either Ad5 or Ad26 vectored vaccines, we should choose Ad26, as we have a lower chance of having a pre-existing immunity against the Ad26, and the blood level of neutralizing antibody to Ad26 is much lower even if we have been infected by Ad26. A low blood level of neutralizing antibody to Ad26 was shown not to reduce the efficacy of vaccines using Ad26.1
Before developing viral vectored vaccines, Harvard Medical school undertook a thorough study on the epidemiology of Ad5 and Ad26 in populations of several nations.1 This study gave them sufficient ground to use Ad26 for their viral vectored vaccines. Therefore, we should have confidence on the efficacy of the vaccine co-developed by the Harvard Medical School and Janssen Pharmaceuticals, which uses Ad26 as a backbone. The vaccine Sputnik V by Gamaleya Research Centre uses Ad5 and Ad26 in the different shots for their 2-shot regimen. The use of Ad26 in one of their vaccines certainly helps to overcome the pre-existing immunity to Ad5 which diminishes the effecacy of the vaccine. On the other hand, the COVID-19 vaccine developed by CanSino uses Ad5 as the vaccine’s backbone; it will be a big challenge for them to market this vaccine to areas with high baseline Ad5 neutralizing antibodies.3
References
1. D.H. Barouch, S.V. Kik, G.J. Weverling, et al. International seroepidemiology of adenovirus serotypes 5, 26, 35, and 48 in pediatric and adult populations. Vaccine. 2011; 29: 5203-5209.
2. S. Zhang, W. Huang, X. Zhou, et al. Seroprevalence of neutralizing antibodies to human adenoviruses type-5 and type-26 and chimpanzee adenovirus type-68 in healthy Chinese adults. J. Med. Virol., 2013 Jun;85(6):1077-84.
3. A big obstacle: Where can CanSino test its vaccine abroad? By Roxanne Liu, and Miyoung Kim. Reuters, July 30, 2020.
In my last blog post, I mentioned that previous infection by a human adenovirus could decrease the efficacy of vaccines that use that adenovirus as a backbone. The best way to avoid using adenovirus vaccines that we may be immune to, is to use a viral vectored vaccine with a non-human adenovirus vector, like the AZD1222 by AstraZeneca and Oxford University, which uses chimpanzee adenovirus. Human populations around the world have a much lower level of pre-existing immunity to the chimpanzee adenovirus.
Alternatively, we can check our serum antibody levels to the adenovirus. However, as most of us are not virology or vaccine experts, we won’t know what is an acceptable level of neutralizing antibodies against the adenovirus used by the vaccine we are thinking of taking.
There were studies performed to check the pre-existing immunity to Adenovirus type 5 (Ad5) and Adenovirus type 26 (Ad26), the two common human adenoviruses used by the adenovirus vectored vaccines for COVID-19, in different populations, by testing the serum neutralizing antibodies to the two adenoviruses. I have put together the data from two of the studies into the table below.1-2 Looking at this data may give us an idea of which type of vaccine to use, if we were given a choice.
| Infection rate of Ad5 and Ad26 in different populations | ||
|---|---|---|
| Country | Seroprevalence of Ad5 (%) | Seroprevalence of Ad26 (%) |
| China | 73.12 | 35.32 |
| Kenya | 90.51 | 66.21 |
| South Africa | 87.9-89.51 | 43.1–53.21 |
| Thailand | 82.21 | 54.61 |
| Uganda | 86.41 | 67.81 |
| United States | ~401 | ~121 |
As we can see from the table, Ad5 infection is generally more common than Ad26 in all the nations studied. The infection rate of Ad5 is at least 50% higher than that of Ad26. Moreover, people in the developing world seems to have higher adenovirus infection rate. Detailed data (not shown in this table) from the results of the multinational study1 also showed a much higher proportion of people with high level of blood antibody against Ad5 in the high Ad5 prevalence areas, in contrast to markedly fewer individuals in these regions demonstrating a high level of blood antibody to Ad26.1 Data also showed that the median level of blood antibody to Ad26 in the 4381 international test participants was approximately 10-fold lower than the median level of blood antibody to Ad5.
The data from the studies did not include populations from all countries around the world, and the studies were done at least 7 years ago. I cannot find any more up-to-date data on studies comparing the prevalence of Ad5 and Ad26 infections. However, the above data gives us a general idea that people in developing countries should try to avoid using Ad5 vectored vaccines. If we were given a chance to choose from either Ad5 or Ad26 vectored vaccines, we should choose Ad26, as we have a lower chance of having a pre-existing immunity against the Ad26, and the blood level of neutralizing antibody to Ad26 is much lower even if we have been infected by Ad26. A low blood level of neutralizing antibody to Ad26 was shown not to reduce the efficacy of vaccines using Ad26.1
Before developing viral vectored vaccines, Harvard Medical school undertook a thorough study on the epidemiology of Ad5 and Ad26 in populations of several nations.1 This study gave them sufficient ground to use Ad26 for their viral vectored vaccines. Therefore, we should have confidence on the efficacy of the vaccine co-developed by the Harvard Medical School and Janssen Pharmaceuticals, which uses Ad26 as a backbone. The vaccine Sputnik V by Gamaleya Research Centre uses Ad5 and Ad26 in the different shots for their 2-shot regimen. The use of Ad26 in one of their vaccines certainly helps to overcome the pre-existing immunity to Ad5 which diminishes the effecacy of the vaccine. On the other hand, the COVID-19 vaccine developed by CanSino uses Ad5 as the vaccine’s backbone; it will be a big challenge for them to market this vaccine to areas with high baseline Ad5 neutralizing antibodies.3
References
1. D.H. Barouch, S.V. Kik, G.J. Weverling, et al. International seroepidemiology of adenovirus serotypes 5, 26, 35, and 48 in pediatric and adult populations. Vaccine. 2011; 29: 5203-5209.
2. S. Zhang, W. Huang, X. Zhou, et al. Seroprevalence of neutralizing antibodies to human adenoviruses type-5 and type-26 and chimpanzee adenovirus type-68 in healthy Chinese adults. J. Med. Virol., 2013 Jun;85(6):1077-84.
3. A big obstacle: Where can CanSino test its vaccine abroad? By Roxanne Liu, and Miyoung Kim. Reuters, July 30, 2020.
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