Study shows coronavirus does not induce cross-protective immune antibodies

According to researchers, patients infected with severe acute respiratory syndrome coronavirus (SARS-CoV) or SARS-CoV-2 generate antibodies that adhere to the other coronavirus; however, the cross-reactive antibodies are not actually cross-protective, as far as cell-culture experiments are concerned.

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Whether or not such antibodies provide cross-protection in the potentiate disease or human body is still a puzzle. The outcomes indicate that additional studies are required to detect parts of the virus that are crucial for inducing a cross-protective immune response.

Since corona virus outbreaks are likely to continue to pose global health risks in the future, the possibility of developing a cross-protective vaccine against multiple corona viruses has been considered.”

Chris Mok, Study Co-Senior Author, University of Hong Kong

Mok continued, “Our findings, albeit limited at present, would suggest that broadly cross-neutralizing antibodies to coronaviruses might not be commonly produced by the human immune repertoire. Moving forward, monoclonal antibody discovery and characterization will be crucial to the development of a SARS-CoV-2 vaccine in the short-term, as well as a cross-protective coronavirus vaccine in the long term.”

From late 2002 to 2003, over 8,000 people across the globe have been infected with SARS, leading to over 700 deaths. SARS-CoV is the virus responsible for this outbreak and shares about 80% of its genomic nucleotide sequence identity with that of the SARS-CoV-2, which is responsible for causing the coronavirus disease 2019 (COVID-19).

In addition, both the coronaviruses enter into and infect the cells in the same manner. In this process, the receptor-binding domain (RBD) of the spike (S) protein, situated on the surface of the coronavirus, adheres to a human cell receptor known as angiotensin-converting enzyme 2, activating the viral fusion with the host cell.

Earlier studies have revealed that protective antibodies against SARS-CoV adhere to the RBD. However, not much is known about the antibody response caused by SARS-CoV-2 infection. It is also not clear how SARS-CoV affects the antibody response against SARS-CoV-2 and the other way round.

Gaining a better understanding of these questions can help develop an effective SARS-CoV-2 vaccine and shed light on whether a vaccine like that would also cross-protect against similar types of viruses.

There are related viruses still circulating in bats, and it is unclear whether any of these may also threaten human health in future, As such, whether infection by one of these viruses cross-protects against another is an important question.”

Malik Peiris, Study Co-Senior Author, University of Hong Kong

To bridge this gap in knowledge, the scientists examined blood samples obtained from 15 Hong Kong-based patients infected by SARS-CoV-2 between 2 to 22 days after the initial occurrence of symptoms.

When compared to the blood samples collected from healthy controls, the five samples obtained from patients 11 days after the onset of symptoms or later had antibodies that can bind to the RBD and other regions of the S protein on SARS-CoV-2 and SARS-CoV.

The team also examined the blood samples obtained from seven patients between 3 and 6 months after the individuals were infected with SARS-CoV.

When compared to blood samples collected from healthy controls, the ones obtained from patients had antibodies that can bind to the RBD and other regions of the S protein on SARS-CoV-2. Collectively, these outcomes reveal that infection with one coronavirus promotes the production of antibodies that can adhere to both RBD and non-RBD parts of the S protein on the other coronavirus.

Through cell-culture experiments, the scientists then tested whether SARS-CoV-2 infection causes SARS-CoV-2-specific neutralizing antibodies, which guard the host cells by preventing the virus from communicating with them.

All the 11 blood samples obtained 12 days or later after the appearance of symptoms had neutralizing antibodies against SARS-CoV-2. However, only a single blood sample had cross-neutralizing antibodies against SARS-CoV, and this was a very weak response.

Likewise, five blood samples collected from SARS-CoV-infected patients had neutralizing antibodies against this virus; however, none could cross-neutralize SARS-CoV-2. The patients’ findings were supported by additional mice experiments.

As such, the clinical implications continue to be elusive. One possibility is that non-neutralizing, cross-reactive antibodies provide cross-protection against viruses present in the body, although they do not protect the cultured cells.

Such a phenomenon has been seen for other types of viruses. Conversely, non-neutralizing antibodies against SARS-CoV-2 may improve viral entry into cells as well as viral replication via a process known as an antibody-dependent enhancement of infection, which has been earlier reported for SARS-CoV.

Whether antibody-dependent enhancement plays a role in SARS-CoV-2 infection needs to be carefully examined in the future. Addressing this question will be critical for developing a safe and effective universal corona virus vaccine.”

Ian Wilson, Study Co-Senior Author, Scripps Research Institute