Antibodies against SARS-CoV-2 induced by prior infection are six times less effective against P.1 variant

Blood plasma from COVID-19 convalescents was tested against Brazilian variant isolates obtained from patients diagnosed in Manaus. The study also assessed the effectiveness of plasma from volunteers immunized with CoronaVac.

By Karina Toledo  |  Agência FAPESP – Laboratory experiments conducted at the University of Campinas (UNICAMP) in the state of São Paulo, Brazil, suggest the antibodies present in the blood plasma of people who have recovered from COVID-19 are six times less capable of neutralizing the Brazilian variant of SARS-CoV-2, labeled P.1, than the B-lineage that circulated in Brazil in the early months of the pandemic.

The study also pointed to low levels of P.1- and B-lineage-neutralizing antibodies in plasma from individuals given the second dose of the CoronaVac vaccine about five months ago. Produced by Chinese pharmaceutical company Sinovac Biotech in partnership with São Paulo’s Butantan Institute, CoronaVac has been administered by the national vaccination campaign in Brazil since mid-January.

The findings are in a paper posted on March 1 to Preprints with The Lancet, a platform for the publication of early-stage research that has not been peer-reviewed. 

“What these preliminary results suggest is that both people who have had COVID-19 and people who have been vaccinated can be infected by P.1 and should continue to take precautions,” said José Luiz Proença Módena, a professor at the university’s Institute of Biology (IB-UNICAMP) and principal investigator for the study.

According to Módena, this phenomenon is common and also occurs with other vaccines, so that some viruses continue circulating even when the population has been immunized. “The findings very much do not suggest that the vaccine doesn’t work,” he stressed.

The experiments described in the article were conducted with support from FAPESP (projects 16/00194-8 and 20/04558-0) at IB-UNICAMP’s Laboratory of Emerging Virus Studies (LEVE), a Biosafety Level III (BSL-3) facility headed by Módena. The group collaborated with the Brazil-UK Center for Arbovirus Discovery, Diagnosis, Genomics and Epidemiology (CADDE), which sent them samples of nasopharyngeal, oropharyngeal or bronchoalveolar secretion from 20 patients infected by the Brazilian variant. They then inoculated the material into cultured cells susceptible to SARS-CoV-2. The presence of P.1 in the patient samples was confirmed by viral genome sequencing.

Two isolates of P.1 obtained from the cultured cells infected in the laboratory were used in the neutralization tests performed on plasma from convalescent patients and vaccinated individuals.

“We already had a collection of plasma donations from people who recovered from COVID-19. They all had high levels of neutralizing antibodies,” Modena told Agência FAPESP. “This material was originally collected and analyzed for the treatment of severe cases [using the method known as passive immunity transfusion or convalescent plasma therapy].”

The convalescent plasma samples, collected two to three months after infection, were tested in parallel against B-lineage and P.1. The results suggested a sixfold reduction in the neutralization of P.1.

“That’s a big number,” Módena said. “In the case of influenza viruses, for example, when a novel variant that’s six times less neutralized by antibodies emerges from one year to the next, this is considered immune escape and the vaccine has to be updated.”

More research needed

The neutralization tests with plasma from vaccinated subjects involved samples donated by eight volunteers who took part in the Phase III trials of CoronaVac and were vaccinated in August-September 2020.

Phase II trials had already shown that the level of neutralizing antibodies in the blood of vaccinated individuals falls sharply after about six months. The in vitro tests performed at IB-UNICAMP also evidenced a weak neutralization effect against both P.1 and B-lineage. However, the researchers stress that these findings should be interpreted with caution because neutralizing antibodies are only one component of the immune system.

“Other forms of protection that can be strongly induced by the vaccine, such as cellular immunity, are probably still capable of keeping vaccinated subjects safe from the disease, especially the severe form. Nevertheless, all the evidence suggests vaccinated people can be infected and transmit the virus,” Módena said.

The study involved a small number of samples, he noted, and the results were not sufficiently robust to justify a finding of the effectiveness of CoronaVac against the Brazilian variant. “More research and in-depth studies are needed to assess the effectiveness of CoronaVac and other vaccines against P.1,” he said.

The researchers stressed that social distancing and hand hygiene remain essential to control transmission of the virus, even among people who have already been infected or vaccinated. “These measures are important to avoid possible cases of reinfection, especially by the emerging novel lineages,” Módena said.

Several students took part in the tests, including William Marciel de Souza, with a scholarship from FAPESP; Karina Bispo dos Santos, with a master’s scholarship; Camila Lopes Simeoni, with a scientific initiation scholarship; and Pierina Lorencini Parise, with a PhD scholarship. The authors of the paper are affiliated with ten universities, including the University of São Paulo (USP) and UNICAMP in Brazil, the University of Oxford in the UK, and Washington University School of Medicine in St. Louis, USA. Besides support from FAPESP, the group received funding from the UK Medical Research Council, the US National Institutes of Health (NIH), UNICAMP’s Teaching, Research and Extension Support Fund (FAEPEX), and several agencies of the federal government of Brazil, such as the Ministry for Science, Technology and Innovation, the Brazilian Innovation Agency (FINEP), the National Council for Scientific and Technological Development (CNPq), and the Ministry of Education’s Coordination for the Improvement of Higher Education Personnel (CAPES).

The article “Levels of SARS-CoV-2 lineage P.1 neutralization by antibodies elicited after natural infection and vaccination” can be accessed at: papers.ssrn.com/sol3/papers.cfm?abstract_id=3793486.