Searching COVID-19 specific antibodies: where is our hope?

antibodies

Antibodies-

Never give up; this is where hope stands. Antibody research is one of the oldest parts of the scientific community.

People who work in this field must know how important this research is! Most of the routine vaccines that we are giving to infants and toddlers are relying on antibodies.

This is usually done by educating the immune system early-life by exposing to a small dose of molecules originated from virus/bacteria, so that the immune system can recognize later and get ready to fight against the actual attack in the future. As science made extraordinary progress during the last decades, antibody research is more focused on the laboratory as a tool to assist other new modern techniques.

People have not forgotten the contribution of antibody research; it is slightly shifted towards a different direction, mainly when new and more complex diseases emerged, and clearly, the role of antibody in that context was questionable. This is because scientists found cell-mediated immune responses are more effective against those diseases like cancer, autoimmune diseases, etc.   

A simple classification of human immunity:

There are two distinct arms in the human immune system that work in collaboration to keep us protected. One is called innate immunity, which is very fast in action but non-specific and knock germs out very efficiently. But innate immune responses are short-lived and cannot remember who attacked first.

Therefore, every time when a person encounters either the same pathogen or a different one, the response likely to be the same. Second, another arm of immunity is called adaptive responses, which are further classified into two groups: cellular and humoral or antibody-driven. This adaptive immunity comes late but could be very specific to a pathogen and can remember when next time a person is exposed to the same pathogen.

Because of this memory total response against the same pathogen is truly fabulous. The most exciting part of these innate and adaptive arms of the immune system is that they work in collaboration by using lots of their potential molecules that are involved in cross-talk. Because of this network that is in place in the human body, viruses, or bacteria are not always successful in establishing infection. 

 

How does the virus gain entry to a human?

Viruses are such a tiny organism that we even could not see without electron microscopy. Although they are small, they could be intense and devastating. One example is the COVID-19 virus; almost all predictions with this pathogen seem to be failed. Interestingly, COVID-19 is not really very different than other COVIDs when the genome sequencing data revealed.

But as you probably know that genomic sequencing only unveils how the genetic codes are organized. It does not tell about what messages you would expect. For example, genetic sequences first transcribe and then translated to make proteins. During this process, end products like proteins undergo many modifications which are important for virus against human-resistance.

One such modification can be seen in a virus envelope, which is like a shell, helping the virus to make negotiations with the prospective host. This enveloped viral surface has major consequences for viral entry because it fuses with host cell membranes together.

Generally, this is thought to be achieved through a complex interaction to a specific cellular host receptor (ACEII receptor) in COVID-19 infection and results in changes in the structure of the viral spike protein that enable forming pores in the host membrane and allows the viral genomes to gain entry into the host cell. Once an entry is achieved, viral replication takes place.

How does antibody help?

It is not known how exactly COVID-19 gain access to the host and under what circumstances, the human immune system either fails or prevent virus entry into the cells. Based on our knowledge with other respiratory viruses, we can just speculate that if a person is not developing symptoms following COVID-19 exposure, it is likely that the innate immunity was successful in expelling the virus. In that case, there are no antibody responses.

If COVID-19 is successful in replication inside the host cells, after infecting alveolar macrophages that are under the lung epithelial lining, there might be an initiation of adaptive immune response by calling other immune cells to come close and start producing antibodies, cytokines, etc. to fight against COVID-19.

Since COVID is likely using the spike protein to bind with the host cell receptor, it a general expectation that a neutralizing antibody (nAb) against viral spike protein would be disrupting the viral entry to the host. Additionally, antibodies can also block viral egress by binding to glycoproteins on the infected cell surface, thus preventing viruses from budding. This is why all of the proposed vaccines against COVID-19 are aimed predominantly to induce antibody responses. Another approach in line is to develop a monoclonal antibody against COVID-19 and use it to treat patients with severe COVID-19.

What is the rationale behind these aggressive ideas?

As I outlined above, how our immune system works and protects us against foreign pathogens, it is the same expectation with COVID-19 that people might generate natural immunity when exposed to COVID-19. Therefore, people either recovered or never developed symptoms but exposed might have that precious protective antibody titers. The good news is that

  1. FDA in the USA already announced the approval of a plasma therapy trial at Johns Hopkins University.
  2. Takeda has announced a polyclonal hyperimmune antigen-purified antibody concentrate.
  3. Regeneron has announced pursuing a monoclonal antibody strategy using its humanized mouse antibody screening platform to produce an antibody cocktail for both therapeutic and prophylactic use.
  4. World Health Organization (WHO) has announced a large-scale effort (named SOLIDARITY II) to aggregate serological data collected in different countries and expects to post results from the initiative within the next few months.

COVID-19 antibody screening and the risk?

Because of the consensus that antibody responses might be the key to block COVID-19, hundreds or more private companies already made kits available in the market suggesting for diagnosis of COVID-19. The same mistakes happened in Bangladesh, where Gono-University motivated the authority to launch an antibody-based diagnosis as a replacement for PCR-based diagnosis.

It is a mistake because of a lack of knowledge of viral immunity in humans and also whether antibody against COVID-19 would be clean or not.

Antibody-based diagnosis is simple and less expensive, but we need to understand the reality because antibody responses against COVID-19 would not be available as detectable levels until 7-14 days post-infection. Interestingly, COVID-19-affected countries now have a feeling that antibody responses in the mass population would soon be useful NOT for diagnosis BUT for screening purposes. Unfortunately, in this direction, markets are flooded by crappy test kits without proper validity tests.

Thus, the FDA recently announced to take this seriously by saying that every kit for antibody detection will undergo scientific review. This action is such an important one because we are at the edge of taking decisions on whether people will go back to normal life sooner or later. The tests will then end up telling people when having antibodies against COVID-19 and when they didn’t, and giving the green signal whether they are immune or not.

We should not be excited about that until we know that having COVID-19 specific antibodies are protective and someone would not get the disease again.

 

Based on all the discussion, it is reasonable to look into antibody levels in the mass people and correlate with their clinical outcomes. Don’t forget that we need a reliable ELISA test that is properly designed and can identify COVID-19 specific antibodies. 

By Dr. Jubayer Rahman (PhD in Infectious Immunology), Maryland, USA

 

 

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