José Módena, from the Unicamp Biology Institute, coordinated work of great repercussion in the country and abroad
Immediate lockdown throughout Brazil and mass vaccination of the population as quickly as possible. This is the flag defended by researcher José Luiz Proença Módena, one of the authors of a study on the Manaus variant (P.1) covered by the main national and international media outlets, such as New York Times, Financial Times e Le Monde. "It is a very delicate moment, the worst of the pandemic, due to a combination of factors: a large number of laboratory confirmed cases of SARS-CoV-2, a large number of deaths and uncontrolled spread of this virus in the national territory, culminating in the emergence of very worrying variants. People have been experiencing this period for a year, they are tired", he ponders.
For Módena, the politicization of confronting the pandemic has hindered different strategies, from non-pharmacological ones, which he considers extremely important, to vaccination ones. "The moment requires that all measures be redoubled. I am completely in favor of the lockdown being adopted immediately throughout the country, and a mass vaccination program. We have a very favorable scenario for the emergence and spread of these variants, due to a series of aspects : a huge population and often with high population density in specific areas, a great diversity of people with very different genetic backgrounds and living conditions, and who are generally not respecting the measures that aim to contain transmission, even if often for a need for subsistence. The virus is circulating freely."
The study published by the platform The Lancet (still in the process of peer review) resulted from experiments conducted by José Módena at the Laboratory for Studies of Emerging Viruses (Leve) at the Institute of Biology (IB) at Unicamp, in partnership with scientists from ten universities, including USP, Oxford ( United Kingdom) and Washington University (St. Louis, USA), as well as CNPEM (National Center for Research in Energy and Materials). The research was supported by several agencies, including Fapesp, Medical Research Council, Ministry of Science, Technology and Innovations (MCTI), Finep, CNPq, Faepex, Capes and NIH.
The results, which are preliminary, show that antibodies present in the blood plasma of people who have already had Covid-19 and recovered, are around six times less efficient in neutralizing the Manaus variant of SARS-CoV-2, compared to the called lineage B, which circulated throughout the country in the first months of the pandemic. The study also shows that the plasma of individuals who received the second dose of CoronaVac, after around five months, also presents a low amount of neutralizing antibodies against the P.1 and B variants. "This phenomenon also occurs with other vaccines, making with some viruses continuing to circulate even after a population is immunized. This, under no circumstances, suggests that the vaccine does not work", highlights the researcher.
José Módena recalls that the discovery of the Manaus variant, in itself, was already a cause for warning, due to its different mutations (there are 10) in the virus's surface protein, the spike protein. "Analyses based on these mutations already indicated the possible existence of a mechanism to escape the action of neutralizing antibodies. Our study does raise this flag, but it needs to be viewed with caution, as it was carried out in an artificial condition (vitro), where we simply incubated the virus with the plasma of people who had had Covid-19, that is, where the antibodies capable of blocking the infection in cells of the original variants that first circulated in Brazil had already been characterized."
The warning brought by the study, reiterates the IB professor, is that people who have already had Covid-19, currently have antibodies with reduced capacity to neutralize the new variant and can, potentially, become reinfected with P.1. "Whether this means that they will have an illness, or a serious illness, we don't know; time and clinical/epidemiological studies will demonstrate it. But the suggestion is that these people can reinfect themselves and, if they reinfect, transmit this virus to those who have never became infected. A similar phenomenon was seen in people vaccinated with CoronaVac. Five months after vaccination, when we incubated the plasma of vaccinated people, we observed that the antibody titer to the two variants, both SarsCov-2 and P.1., was very low."
The researcher also commented on the possibility of adapting existing vaccines, for example, for P.1, clarifying that the reformulation process depends on how the vaccine is manufactured. "A parenthesis is in order here: CoronaVac is an inactivated, non-infectious virus, which has its structure preserved; all portions capable of dissipating an immune response will be present, that is, it is one of the vaccination strategies with the lowest chance of escape of neutralization or other immunological escape mechanisms. When we assume that there may be antibody escape from a vaccinated person - which is not proven in the study - it does not mean that the new variant will cause disease in vaccinated people. The immune response triggered by a vaccine as CoronaVac is much larger and more complex than the production of neutralizing antibodies: we still have fragments of the virus, viral antigens presented to lymphocytes that can generate cellular memory of response."
Módena considers CoronaVac a vaccine strategy with great potential to stop the development of serious forms of the disease, even through new variants. However, it is a more complex vaccination strategy to be redone if necessary, which means that monitoring the immune response in vaccinated people needs to be monitored in real time. "This is because it is necessary to start the process from scratch, starting with the production of the active pharmaceutical ingredient (IFA), which is actually a new virus. It is a process that takes longer, but the chance of loss of effectiveness is much lower. Other strategies are based on the expression or administration of messenger RNA, or modified viruses so that the body produces that viral protein, aiming mainly at the production of neutralizing antibodies against the virus's spike protein - this is the strategy adopted by Moderna and even by Astrazeneca. The reformulation process is much faster, changing the target and generating a new vaccine, according to the companies, in an average interval of three months."
Complementary study
The Unicamp researcher contributed with suggestions in the review process and is among the authors of another study that has synergistic results to what was discussed and that narrates the emergence and spread of the P.1 variant in Manaus. This study was coordinated by Professor Ester Sabino, from the Institute of Tropical Medicine at USP, and Professor Nuno Faria, from Imperial College in London, and in the end brings results based on mathematical modeling that suggest that the new variant would be capable of circumventing the system immune system of already infected people. "It is a very well designed, elegant study, in which the authors characterize P.1, the mutations that cause concern, the likely dates of its emergence, the spread in Manaus, its proportion compared to other variants and the increase in this proportion to become one of the most prevalent and in a very short time."
The mathematical models in this study, says José Módena, indicate that the high transmissibility of P.1 compared to other variants may be associated with a higher viral load in infected people and the escape of the immune system, or at least the activity of neutralizing antibodies. One of the indications is the high rate of infection by P.1 in a population with a high rate of seroconversion (or that have anti-SARS-CoV-2 antibodies), such as that of Manaus, suggesting that people already infected by SARS-CoV-2 1 (even if silently) can be reinfected by the new variant. This data goes in line with what we showed in our study, I think both are complementary. But, again, clarifying that this study is based on P.XNUMX dispersal models. over time, and the other is a laboratory study (vitro). Both are suggestive, neither is confirmatory.”
The study Levels of SARS-CoV-2 lineage P.1 neutralization by antibodies 2 elicited after natural infection and vaccination it's at https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3793486.
