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The expected effect of vaccines

Administering vaccines on a large scaled will tell us whether, in addition to protecting against the disease, they are also able to prevent infection by SARS-CoV-2

Alexandre Affonso

Immunization against COVID-19, the disease caused by the novel coronavirus, is progressing worldwide, bringing us closer to overcoming the current health crisis. As the process advances, we will learn more about the effect of the approved vaccines. One aspect that will become more clear over time is whether as well as protecting people from the diseease, they are also able to prevent infection by SARS-CoV-2 virus itself. Clinical studies on the vaccines in use show that they are effective at inhibiting the disease, reducing symptoms, and preventing severe outcomes, but it is not yet known whether they can also prevent the virus from invading human cells and starting the replication process. Vaccines that prevent both disease and infection induce what doctors call sterilizing immunity.

There is a subtle but important difference between stopping the infection, and consequently the disease, and protecting only against the disease. Vaccines that prevent the onset of COVID-19 do not necessarily prevent immunized people from being infected and transmitting the novel coronavirus, even if they present no symptoms and feel fine. Those that totally block the infection, providing sterilizing immunity, however, nullify the virus and interrupt the chain of contagion.

British virologist Sarah Caddy, a clinical researcher at the Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID) at the University of Cambridge, UK, says the ideal scenario would be that all vaccines prevent infection by the pathogen, but in practice, this is not the case. Most existing vaccines only prevent onset of the disease. This is the case, for example, with the vaccines for influenza, hepatitis, measles, tuberculosis, and rotavirus.

“Even without blocking infection,” Caddy told Pesquisa FAPESP, “it is possible to reduce transmission and stop the COVID-19 pandemic.” This is because a vaccinated person, if infected with the novel coronavirus, will have a lower viral load than someone who has not been immunized, catches the virus, and shows symptoms. Studies indicate that asymptomatic infected people also have a lower viral load. Vaccines thus help to reduce the virus’s circulation rate, explains the expert. “Even without sterilizing immunity, a vaccine can control the disease in the population.”

According to infectious disease specialist Raquel Stucchi of the School of Medical Sciences (FCM) at the University of Campinas (UNICAMP), the current COVID-19 vaccines can help us achieve herd immunity, where the spread of the virus is contained because there are so few people susceptible to contracting it. “It is possible to achieve herd immunity against the novel coronavirus even without having complete control over its transmission. To do so, we need to vaccinate a larger contingent of the population,” says Stucchi. “Of course, it would be a great help if we had a vaccine that also prevents transmission, but it is not essential. Today we have several vaccines in our portfolio that despite not conferring sterilizing immunity, are capable of controling the disease for which they were developed.”

Neutralizing antibodies
The challenge of formulating vaccines with sterilizing potential lies in the fact that they need to stimulate our immune system to produce large quantities of a specific type of antibody, known as neutralizing antibodies, which are able to bind to key points of the virus’s surface proteins that are used by the pathogen to enter the host cell.

“Antibodies that bind specifically to key points on these proteins or accessory proteins that mediate the virus’s entry into the cell neutralize the viral infection by preventing the virus from passing from the extracellular fluid into the cell,” explains virologist Fernando Spilki, former president of the Brazilian Society of Virology and a professor at Feevale University in Novo Hamburgo, Rio Grande do Sul. “Thus, they completely inhibit viral replication. As a result, they promote an immunity that is effectively sterilizing, since they prevent the infection from spreading inside the body and producing viral particles in large quantities, which is associated with disease and contagion.”

In the case of COVID-19, says Caddy, to promote sterilizing immunity, vaccines need to induce the production of neutralizing antibodies that bind to the virus’s spike protein (also known as the S protein), specifically to a ligand called the receptor binding domain (RBD), adds Spilki. “This objective [blocking the RDB and providing sterilizing immunity], although difficult to achieve, is the basis for the design of vaccines that use adenoviral vectors, such as AstraZeneca’s compound, and mRNA, such as Pfizer’s and Moderna’s,” notes the Feevale researcher.

In June 2020, a team led by Brazilian immunologist Michel Nussenzweig, from the Rockefeller University in New York, USA, published an article in the journal Nature showing that not all COVID-19 patients analyzed in the study conducted by his group produced the same antibodies, and that neutralizing antibodies were rare and found in large quantities in only a few people. The paper concluded that an efficient vaccine would stimulate the production of these antibodies.

In terms of structure and classification, neutralizing antibodies are part of the same classes and subclasses as the IgG, IgM, IgA, IgE, and IgD immunoglobulins that comprise our humoral immunity (see Pesquisa FAPESP issue no. 294), but they belong primarily to the IgG class, and to a lesser extent, the IgM class.

Experts highlight that it is also important for vaccines to induce the production of neutralizing IgA antibodies, the type found on the surfaces of mucous membranes in our airways, which the virus uses to enter the body. “In order to stimulate a more robust response and block the infection, we will probably need different classes of antibodies capable of recognizing the virus,” concludes the Cambridge researcher.

Scientific Article
ROBBIANI, D. F. et al. Convergent antibody responses to SARS-CoV-2 in convalescent individuals. Nature. June 18, 2020.