Omicron and the Vaccine Challenge

WHO acted promptly in nominating omicron A variant of great caution, not because little was known about how it spread or how severe disease it causes, but because of its many mutations that potentially make the virus different from known forms. allows it to work.

Several countries in the world have taken drastic measures including halting travel from African countries where the variant has been observed. Travel restrictions are controversial and should only be enforced judiciously and for a short period of time until more is known about the clinical and transmission characteristics of a type. If there is covert spread in the community and cases appear with no clear travel history to affected countries, they are of limited utility. a travel ban established after community spread It is like closing the barn door after the horse has already bolted. South Africa has a world-class infectious disease surveillance system, which has allowed the country to identify the variant and report it very quickly. Now that the country is facing financial crunch due to restrictions on travel, many feel that they are being punished unnecessarily for doing the right thing.

Omicron is highly mutated, meaning it has many changes in its genetic material compared to the original SARS-CoV-2 virus identified in Wuhan, China. It also has many more mutations than the prevalent forms of anxiety. Some of these changes may have no biological significance, but others are likely to result from changes in the amino acid building blocks of proteins. This does not mean that it is a different virus entirely, but rather that some biological characteristics may differ.

Proteins are the workhorse molecules of life. SARS-CoV-2 contains more than two dozen proteins. The one you hear about most is the spike protein because it allows the virus to enter cells and is also a target for antibodies produced after vaccination. The spike protein is found in an array on the surface of the virus where it acts as a “key” that opens human cells that contain a specific “lock” called the ACE2 receptor. The key to the virus first identified in Wuhan fits the cellular lock well (and better than the original SARS coronavirus). This was one of the reasons why it was able to cause a pandemic.

But as the virus infected more people, it changed randomly and its ability to move inside cells and make copies of itself improved. This led to better viral replication and, in a way, better transmission efficiency. delta Which became effective worldwide in 2021. Some changes led to more reinfection and reduced recognition by antibodies produced from approved vaccines. We don’t know much about Omicron yet, but those are our concerns with this new version.

A weak immune response?

The vaccines currently being used were created to elicit an immune response against the virus identified in Wuhan. As viruses mutate and change shape over time, the symptoms recognized by antibodies produced after infection or vaccination also change. This does not mean that the variants become vaccine-proof. This could mean that a booster dose or a modified vaccine that recognizes the changes would need to be administered to provide complete protection.

Currently, we do not know the extent of protection for people who have been fully vaccinated against Omicron. We do not know how well the variant spreads in a vaccinated population while a vaccine has not been administered. Scientists are running to find answers to these questions. As soon as we get the information, we will find out in the real world how many people who were vaccinated are getting infected with Omicron. Here too, preliminary data from South Africa indicates that uninfected people are more likely to be infected.

Researchers will first test how well antibodies are able to neutralize the variant from blood samples from people who have been previously vaccinated. Vaccines were created to generate polyclonal antibodies that recognize different parts of the spike protein. If the protein is changed significantly, the recognition by the antibody will be reduced. Because of its wide variations, it is likely that antibodies will show a low neutralizing ability against Omicron. If the amount of antibodies decreases with the variant, one option is to introduce a booster of the earlier vaccine at the same dose or even at a higher dose to “top-up” antibody levels. Vaccine manufacturers are testing this approach.

It is worth noting that the detection of antibodies has decreased with other variants as well. The extent to which antibodies block infection varies from person to person. The drop in deactivation ability can also vary. Loss of inactivation should not be compared with total loss of immunity.

Another important point: neutralization experiments err on the side of caution, because they do not consider cell-mediated immunity, the second arm of the immune response that begins to prevent serious disease. If antibodies are the army of the immune system, then humans also have a navy and an air force.

Complete abrogation of an immune response is possible with a heavily mutated virus, but this seems impossible based on current knowledge. As with other SARS-CoV-2 types, in addition to antibodies, other components of the immune system such as T cells help reduce the severity of infection after vaccination.

In the coming weeks, more will be known about the Omicron version, but vaccine makers already have a head start. They have started working on modified vaccines. Vaccine manufacturers are also making bivalent vaccines that recognize parts of different types. As more types emerge in the future, annual boosters with modified vaccines may be necessary. The ultimate hope is that super-vaccines that recognize different types of parts and different coronaviruses will be available in a few years.

Especially mRNA vaccines are easy to adapt because the delivery mechanism remains the same. Only “message” needs to be modified. Pfizer has indicated it may ship the first batch of any new vaccines (should one be required) in 100 days. Viral-vectored vaccines (such as Oxford/AstraZeneca/Covishield) are easy to design but require a bit more work for mass production.

It is not yet known how other people will be infected if they come into contact with Omicron. The immune response after infection is heterogeneous and depends on several factors including age, health, and whether the infection was asymptomatic or symptomatic. But unlike most vaccines, antibodies will be produced after natural infection to other proteins of the virus in addition to the spike protein.

Inactivated virus vaccines produce antibodies to parts of the virus in addition to the spike protein. Although these cannot prevent infection (since the spike protein is the major viral protein that mediates this phase), they can reduce disease severity. Covaxin, which is an inactivated virus vaccine, may be sustainable in preventing serious disease against Omicron. However, it warrants further investigation.

drugs may still work

Convalescent plasma has not been found to work for SARS-CoV-2 or any other variant and should not be used for Omicron. Monoclonal antibodies targeting the spike protein will need to be updated because they are very specific for parts of the coronavirus spike protein.

A silver lining is that drugs currently being used to treat COVID-19 (or are in late-stage clinical trials) are not expected to be adversely affected by Omicron because they are viral. Spikes do not target proteins. Most of the mutations in Omicron that have gathered interest are in the spike protein but are mutations in other viral proteins, so this will still need to be tested.

Merck’s molnupiravir is an oral antiviral that thwarts the viral replication process. The drug is a dummy for a key piece that is needed to insert the virus into its genetic material as it makes copies inside cells. Molnupiravir gets embedded in the viral RNA and hence the defective viral parts are formed. And the drug generally appears to be resistant to varying degrees. In some ways, the mode of action of molanupiravir is similar to that of the earlier antiviral, remdesivir. However, molanupiravir is available in pill form. There is some debate about the efficacy of molanupiravir (and Merck recently reported a 50% to 30% reduction in risk). Other tests conducted in India by other companies were put on hold.

Pfizer contains a combination antiviral that targets a different protein called main protease. The main protease is an enzyme that coronaviruses require to infect cells, so it is an attractive drug target. This therapy uses ritonavir, an antiviral previously used for HIV, and combines it with a new small molecule that originated in Pfizer’s own laboratories. It is an oral antiviral designed to be used at the first sign of infection. If approved, it could serve as a line of defense against Omicron as well as other forms.

Approved steroid drugs such as dexamethasone have limited indications for use in severe COVID-19, but are also unlikely to be affected by Omicron.

Omicron’s severity

Preliminary reports from South Africa and elsewhere have led to speculation that the disease caused by Omicron is clinically minor. This will be great news because the severity of symptoms will ultimately determine the rigor of the public health response. However, the demographics of the population also matters as we know that COVID-19 does not affect all populations equally. Young, healthy people are more likely to have mild COVID-19 regardless of its type. South Africa has a relatively young population compared to many other countries.

It is tempting to think that the clinical symptoms are mild, but whether this is due to the biological properties of the virus is not yet known. The severity of an infectious disease is determined not only by the virus itself, but also by the health and immune response of the host and environment.

Unless multiple infections have been studied, it is difficult to determine the clinical severity of a virus, which presents itself differently across the spectrum from asymptomatic to severe COVID-19. South Africa is 25% vaccinated and has gone through several Covid-19 waves with earlier variants. If the rate of re-infection is relatively high, then those are the cases in which we would expect less severe symptoms (assuming there was some immune protection from earlier types).

Omicron replaced other variants that have been sequenced in South Africa, but the country was going through a decline in cases at the time. Whether the current increase is due to more transmissions with Omicron will not be known until the spread of the variant is tracked over a longer period of time. Some types arise because of accidental events, and do not eventually outweigh others.

Epidemiological studies will trace the spread of Omicron where the delta is already established. If there is no difference in the way people interact and the percentage of infections with Omicron increases, it will mean that this version is overtaking Delta. This would certainly be a matter of concern.

Meanwhile, vaccinated people should wear appropriately fitting masks, practice social distancing and avoid crowded places. Current vaccines cannot prevent infection or prevent mild or moderately symptomatic COVID-19. But they will continue to serve their main purpose if they can keep people away from hospitals and prevent deaths.

Anirban Mohapatra, a microbiologist by training, is the author of COVID-19: Separating Fact from Fiction. These are his personal views.