SARS-CoV2
If I have had COVID-19 already, do I need to get the vaccine and why?

If I have had COVID-19 already, do I need to get the vaccine and why?

Question from a follower: If I have had COVID-19 already, do I need to get the vaccine and why?

The simple answer is yes.

Antibodies to SARS-CoV-2 have been shown to decrease over time, with some individuals losing measurable antibodies as soon as 6 months post-infection. While there isn’t a lot of data as to whether the lack of circulating immunoglobulins means that the individual is again susceptible to the virus, there have been a few reported cases where individuals have had re-infections which may indicate this as a possibility. There are other questions about whether the lack of circulating antibodies may not be indicative of a loss of infection (see this article by Cox and Brostad (2020), which looks into why the lack of circulating antibodies may only be part of the story)

https://doi.org/10.1038/s41577-020-00436-4

There are a few different theories as to why it is important to be vaccinated, even if you have already been infected with SARS-CoV-2. I want to talk briefly about one of them, and then give a little explanation of why this is important.

SARS-CoV-2 is a beta-coronavirus (CoV) and shares similar structures to the original SARS, MERS, and other coronaviruses. The main structures of the coronaviruses include five (5) primary structures: Spike Protein (Protein S), Membrane Protein (Protein M), Envelope Protein (Protein E), Nucleocapsid Protein (Protein N), and RNA (see image)

Image Source: https://doi.org/10.1038/s41433-020-0790-7

Each of these proteins can be an antigen, and the body is theoretically capable of developing antibodies in response to any or all of the proteins, but in practice, we predominantly develop immune responses to Protein N and Protein S almost exclusively (https://doi.org/10.1111/mec.15730). Even with the primary immunological targets being the nucleocapsid and the spike protein, the body’s humoral response (B Cells) heavily focuses on the nucleocapsid protein. There are multiple antigenic sites on each of the proteins, allowing the proteins to be targeted by both cellular (T-Cell et al.) and humoral (B-Cell, Immunoglobulins et al.) action.

https://doi.org/10.1111/mec.15730

One study by Huang et al. (2004) found that over 95% of individuals tested developed N protein-specific antibodies to the original SARS, while less then 50% of individuals developed S protein-specific antigens (https://doi.org/10.1002/jmv.20096). With SARS-CoV-2, Burbelo et al. (2020) found slightly different values, such that N protein-specific antigens were present 100% of the time > 14 days post infection, while S protein-specific antigens were present 91% of the time in the same timeframe in their sample of RT-PCR positive individuals (https://doi.org/10.1093/infdis/jiaa273).

https://doi.org/10.1002/jmv.20096

https://doi.org/10.1093/infdis/jiaa273

Where this gets interesting is the antigenic drift (small mutations and changes) seen with SARS-CoV-2. When we look at the changes seen in SARS-CoV-2 over the last 12 months, there are few changes to Protein S and moderate changes to Protein N. Of the changes which have been discovered to Protein S, none of these changes have significantly altered the protein, nor have they changed the antigen binding sites (https://doi.org/10.1111/mec.15730). Forni et al. (2020) found that the spike protein mutation D614 has increased the infectious capacity but hasn’t changed the antigen sites.

https://doi.org/10.1111/mec.15730

Since the main humoral target for SARS-CoV-2 is the nucleocapsid protein and the nucleocapsid protein has moderate antigenic drift, there is a possibility that mutations to Protein N could allow re-infection without the loss of antibodies. A second factor is that many individuals will have a minor encounter with the virus, which could result in a lower level of immunoglobulins.

By vaccinating against a singular protein (Protein S) which has low antigenic drift, we are able to ensure that the body is able to recognize both the virus and viral-infected cells. Targeting a single protein also allows the body to focus a higher response focused on a smaller number of antigenic sites. Even with the genetic changes that have been seen on the spike protein, they haven’t altered the antigen targets and hence they don’t affect the antigenicity of the virus. This combination of a single protein structure combined with low antigenic changes, should allow a higher immune response (and longer lasting) combined with a longer lasting (less possibility of mutation) immunity.

For more information on Antigenic Drift and Shift, see the Khan Academy video here: https://www.youtube.com/watch?v=Ubp-Dz5uGUk

Image Source: https://doi.org/10.1038/s41433-020-0790-7

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