After the disinformation on nanoparticles, on mortality and adverse effects, on the trial phases or the link with strokes, opponents of vaccines against Covid-19 continue to spread new misleading arguments.
The latest concerns a rare but already observed immune mechanism with certain vaccines: the facilitation of infection by antibodies. Since they discovered its existence, anti-vaccine claim that vaccines against Covid-19 not only do not protect their hosts, most worsen their state of health, which would explain, according to them, the unprecedented wave of contamination in Europe. But these claims are not based on any scientific observation.
What are facilitative antibodies?
Facilitating antibodies are antibodies which, instead of neutralizing the virus, will facilitate its replication and, therefore, the infection of new cells. They are no different from the neutralizing antibodies usually made by the human immune system. Once produced by the B lymphocytes, the antibodies will identify the coronaviruses present nearby and bind to them physically, by attaching themselves to their surface protein (the spicule, or the spike protein). Nothing abnormal, so far. These antibodies then recruit immune cells which will phagocytose the virus to destroy it.
By binding to the virus, the antibodies have the function of “recruiting” immune cells, which will destroy the virus.
Classically, the antibodies linked to a virus “attach” to a macrophage via its receptor (called FcγR), the macrophage “swallows” and “digests” everything (these are the endocytosis and lysis phases ). However, in the case of an infection facilitated by antibodies, at the time of endocytosis, the neutralizing chemical bond between the antibodies and the virion may prove to be fragile and “break”; the virion then “escapes” and can then infect the macrophage, in which it replicates, as in a Trojan horse.
The infection can also be facilitated by an overreaction of the immune system caused by the antibodies. By binding to the virus, these have the function of “recruiting” immune cells, which will destroy the virus. But this recruitment sometimes causes a chain reaction of immune cells and extreme inflammation that will backfire on the body. Respiratory pathogens often drive this activation pathway.
The facilitations of infection by antibodies occur mainly during a second viral infection, in subjects already infected but who encounter a different strain from the first virus they crossed. Exposure to a virus that is almost identical but whose surface proteins are different weakens the neutralizing capacity of the antibodies.
Cases of facilitated posterior infections have been documented for certain human coronaviruses, including SARS-CoV-1, the virus responsible for the SARS pandemic in 2003. But the vast majority of known cases concern the dengue virus.
The example of Dengvaxia in the Philippines
These facilitated infections can be dangerous and upset the risk-benefit balance of a vaccine to the point of canceling its marketing authorization. This is what happened with the vaccine against dengue fever (Dengvaxia) developed by Sanofi-Pasteur. It was suspended in December 2017 in the Philippines, after the laboratory warned the government that children who had never been infected with the disease were at particular risk if they encountered the virus after vaccination, instead of be protected by it. Dengue virus has five different serotypes, and it is common for a second natural infection with a different serotype to cause a more serious infection due to insufficiently neutralizing antibodies. It is this mechanism that has been observed with Dengvaxia.
The balance sheet of the case is not easy to establish. Nineteen deaths from dengue fever in vaccinated minors have been recorded, without the link with the vaccine having been medically established. Philippine authorities, who have taken legal action against Sanofi, say they are investigating more than 600 deaths directly caused by the vaccine. However, the figure, methods and technical explanations advanced by the authorities did not convince the Filipino medical community or dengue fever experts.
Occasionally, infections have been facilitated by vaccines targeting other viruses:
- Some older measles vaccines using an inactivated version of the virus sometimes caused more serious infection after vaccination. They are no longer used and have been replaced by those using an attenuated but live version of the virus.
- A vaccine developed in the 1960s against respiratory syncytial virus, the most common cause of lung infection in infants, had the same problems with the inactivated virus. Its development was stopped and never came to fruition.
The rare facilitations of infection by antibodies reported in the history of vaccinology have most often been caused by inactivated or even attenuated virus vaccines, as in the case of Dengvaxia.
What about the Covid-19 and its vaccines?
Facilitated infections have already been suspected in some cases of Covid-19. Recent work by a Chinese team published in the journal Viruses in December 2021 showed in vitro traces of facilitated infections in the sera of convalescent patients. The case of a 25-year-old American infected twice in two months with two variants of SARS-CoV-2, with a more severe infection the second time, was described in October 2020 in The Lancet. A higher viral load or a more virulent virus may explain the clinical severity of the second infection, but the authors do not exclude that it could have been an infection facilitated by the antibodies.
The risk of triggering facilitated infections in vaccinated populations was a topic of discussion in the scientific community during the development phase of the current vaccines, in early 2020. Researchers wanted to minimize the risks by targeting as specifically as possible the spike protein of SARS-CoV-2, so that the neutralizing activity of the antibodies produced remains sufficient to avoid facilitations of infection. Data from clinical trials of the two messenger RNA vaccines from Pfizer-BioNTech and Moderna published in the fall of 2020 do not indicate any cases of infection facilitated by vaccination.
The cases described in the medical literature remain very rare, and such a mechanism has not been observed in SARS-CoV-2 infections or among the vaccinated population. A single publication, dated September 2021, diverges from the relative existing consensus, but it only reports indirect observations which prove nothing and do not convince the community of immunologists. It has not been taken up by any other study and is only cited on social networks by antivaccines.
If vaccines against Covid-19 or contaminations by SARS-CoV-2 facilitated and aggravated subsequent infections, pharmacological monitoring and the scientific community would have already observed and documented this, even at a low frequency. However, it is not the case. On the contrary, all the data accumulated in real life on current vaccines show a significant level of protection against severe forms of the disease.
In France, data from the research, studies, evaluation and statistics department, which cross-reference hospital data with those on vaccination status, indicate that vaccinated persons are largely under-represented among the serious forms: equal population, they are nine times less present than the non-vaccinated and fourteen times less admitted to critical care than the latter. Those vaccinated with a booster are even less so. This huge gap between the vaccinated and the non-vaccinated among the severe or fatal forms of Covid-19 was also observed in the United States from November 2021, but also in Switzerland, Chile, or England.