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SARS-CoV-2 infection protects against rechallenge in rhesus macaques

Science

One of the many open questions about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is whether an individual who has cleared the virus can be infected a second time and get sick. Chandrashekar et al. and Deng et al. generated rhesus macaque models of SARS-CoV-2 infection and tested whether natural SARS-CoV-2 infection could result in immunity to viral rechallenge. They found that animals indeed developed immune responses that protected against a second infection. Although there are differences between SARS-CoV-2 infection in macaques and in humans, these findings have key implications for public health and economic initiatives if validated in human studies. Science , this issue p. [812][1], p. [818][2] An understanding of protective immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical for vaccine and public health strategies aimed at ending the global coronavirus disease 2019 (COVID-19) pandemic. A key unanswered question is whether infection with SARS-CoV-2 results in protective immunity against reexposure. We developed a rhesus macaque model of SARS-CoV-2 infection and observed that macaques had high viral loads in the upper and lower respiratory tract, humoral and cellular immune responses, and pathologic evidence of viral pneumonia. After the initial viral clearance, animals were rechallenged with SARS-CoV-2 and showed 5 log10 reductions in median viral loads in bronchoalveolar lavage and nasal mucosa compared with after the primary infection. Anamnestic immune responses after rechallenge suggested that protection was mediated by immunologic control. These data show that SARS-CoV-2 infection induced protective immunity against reexposure in nonhuman primates. [1]: /lookup/doi/10.1126/science.abc4776 [2]: /lookup/doi/10.1126/science.abc5343


Development of an inactivated vaccine candidate for SARS-CoV-2

Science

Global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to an urgent race to develop a vaccine. Gao et al. report preclinical results of an early vaccine candidate called PiCoVacc, which protected rhesus macaque monkeys against SARS-CoV-2 infection when analyzed in short-term studies. The researchers obtained multiple SARS-CoV-2 strains from 11 hospitalized patients across the world and then chemically inactivated the harmful properties of the virus. Animals were immunized with one of two vaccine doses and then inoculated with SARS-CoV-2. Those that received the lowest dose showed signs of controlling the infection, and those receiving the highest dose appeared more protected and did not have detectable viral loads in the pharynx or lungs at 7 days after infection. The next steps will be testing for safety and efficacy in humans. Science , this issue p. [77][1] The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in an unprecedented public health crisis. Because of the novelty of the virus, there are currently no SARS-CoV-2–specific treatments or vaccines available. Therefore, rapid development of effective vaccines against SARS-CoV-2 are urgently needed. Here, we developed a pilot-scale production of PiCoVacc, a purified inactivated SARS-CoV-2 virus vaccine candidate, which induced SARS-CoV-2–specific neutralizing antibodies in mice, rats, and nonhuman primates. These antibodies neutralized 10 representative SARS-CoV-2 strains, suggesting a possible broader neutralizing ability against other strains. Three immunizations using two different doses, 3 or 6 micrograms per dose, provided partial or complete protection in macaques against SARS-CoV-2 challenge, respectively, without observable antibody-dependent enhancement of infection. These data support the clinical development and testing of PiCoVacc for use in humans. [1]: /lookup/doi/10.1126/science.abc1932


Isolation of potent SARS-CoV-2 neutralizing antibodies and protection from disease in a small animal model

Science

Antibodies produced by survivors of coronavirus disease 2019 (COVID-19) may be leveraged to develop therapies. A first step is identifying neutralizing antibodies, which confer strong protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Rogers et al. used a high-throughput pipeline to isolate and characterize monoclonal antibodies from convalescent donors. Antibodies were selected for binding to the viral spike protein, which facilitates entry into host cells by binding to the angiotensin-converting enzyme 2 (ACE2) receptor. Most isolated antibodies bound to regions of the spike outside of the receptor binding domain (RBD); however, a larger proportion of the RBD-binding antibodies were neutralizing, with the most potent binding at a site that overlaps the ACE2 binding site. Two of the neutralizing antibodies were tested in Syrian hamsters and provided protection against SARS-CoV-2 infection. Science , this issue p. [956][1] Countermeasures to prevent and treat coronavirus disease 2019 (COVID-19) are a global health priority. We enrolled a cohort of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–recovered participants, developed neutralization assays to investigate antibody responses, adapted our high-throughput antibody generation pipeline to rapidly screen more than 1800 antibodies, and established an animal model to test protection. We isolated potent neutralizing antibodies (nAbs) to two epitopes on the receptor binding domain (RBD) and to distinct non-RBD epitopes on the spike (S) protein. As indicated by maintained weight and low lung viral titers in treated animals, the passive transfer of a nAb provides protection against disease in high-dose SARS-CoV-2 challenge in Syrian hamsters. The study suggests a role for nAbs in prophylaxis, and potentially therapy, of COVID-19. The nAbs also define protective epitopes to guide vaccine design. [1]: /lookup/doi/10.1126/science.abc7520


Serology assays to manage COVID-19

Science

In late 2019, China reported a cluster of atypical pneumonia cases of unknown etiology in Wuhan. The causative agent was identified as a new betacoronavirus, called severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2), that causes coronavirus disease 2019 (COVID-19) (1). The virus rapidly spread across the globe and caused a pandemic. Sequencing of the viral genome allowed for the development of nucleic acid–based tests that have since been widely used for the diagnosis of acute (current) SARS-CoV-2 infections (2). Development of serological assays, which measure the antibody responses induced by SARS-CoV-2 infection (past but not current infections), took longer.


Rapid COVID-19 vaccine development

Science

The trimeric spike protein is the primary target for vaccine-induced antibodies intended to block virus attachment to the human angiotensin-converting enzyme 2 (ACE2) receptor. Rapid development of a vaccine to prevent coronavirus disease 2019 (COVID-19) is a global imperative, and defining the stakes and potential hurdles is critical because regulatory and medical decisions are based on benefit:risk calculations. The ability of viruses to achieve pandemic spread is diminished by establishing higher levels of community (herd) immunity, and a key question is whether protection against severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2) will happen by widespread deployment of an effective vaccine or by repeated waves of infection over the next few years until 60 to 70% of people develop immunity. Because the human population is naïve to SARS-CoV-2, the consequences of repeated epidemics will be unacceptably high mortality, severe economic disruption, and major adjustments to our way of life. Therefore, the benefit of developing an effective vaccine is very high, and even greater if it can be deployed in time to prevent repeated or continuous epidemics.