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Insular communities are particularly vulnerable to anthropogenic extinctions and introductions. Changes in composition of island frugivore communities may affect seed dispersal within the native plant community, risking ecological shifts and ultimately co-extinction cascades. Introduced species could potentially mitigate these risks by replacing ecological functions of extinct species, but conclusive evidence is lacking. Here, we investigate changes in plant–frugivore interactions involving frugivorous birds, mammals and reptiles in Mauritius, an oceanic island with an exceptionally well-specified frugivore community and well-described species introduction history. We demonstrate substantial losses of binary interaction partnerships (at the species level) resulting from native species extinctions, but also gains of equal numbers of novel interactions with introduced species, potentially supporting the idea that non-native species might compensate for lost seed dispersal. However, closer investigation of animal seed handling behaviour reveals that most interactions with seed dispersers are replaced by ecologically different interactions with seed predators. Therefore, restoration of seed dispersal functionality in this novel plant–frugivore community is unlikely. Many plant species depend on frugivores for seed dispersal. Here, the authors investigate plant-frugivore networks in Mauritius, finding that the new interactions gained from the arrival of non-native seed predators are unlikely to compensate for the extinction of seed dispersers.

Global change and human expansion have resulted in many species extinctions worldwide, but the geographic variation and determinants of extinction risk in particular guilds still remain little explored. Here, we quantified insular extinctions of frugivorous vertebrates (including birds, mammals and reptiles) across 74 tropical and subtropical oceanic islands within 20 archipelagos worldwide and investigated extinction in relation to island characteristics (island area, isolation, elevation and climate) and species’ functional traits (body mass, diet and ability to fly). Out of the 74 islands, 33 islands (45%) have records of frugivore extinctions, with one third (mean: 34%, range: 2–100%) of the pre-extinction frugivore community being lost. Geographic areas with more than 50% loss of pre-extinction species richness include islands in the Pacific (within Hawaii, Cook Islands and Tonga Islands) and the Indian Ocean (Mascarenes, Seychelles). The proportion of species richness lost from original pre-extinction communities is highest on small and isolated islands, increases with island elevation, but is unrelated to temperature or precipitation. Large and flightless species had higher extinction probability than small or volant species. Across islands with extinction events, a pronounced downsizing of the frugivore community is observed, with a strong extinction-driven reduction of mean body mass (mean: 37%, range: –18–100%) and maximum body mass (mean: 51%, range: 0–100%). The results document a substantial trophic downgrading of frugivore communities on oceanic islands worldwide, with a non-random pattern in relation to geography, island characteristics and species’ functional traits. This implies severe consequences for ecosystem processes that depend on mutualistic plant–animal interactions, including ecosystem dynamics that result from the dispersal of large-seeded plants by large-bodied frugivores. We suggest that targeted conservation and rewilding efforts on islands are needed to halt the defaunation of large and non-volant seed dispersers and to restore frugivore communities and key ecological interactions.

We provide an overview of the current state of knowledge of island frugivory and seed dispersal and identify knowledge gaps that are important for fundamental research on—and applied conservation of—island ecosystems. We conducted a systematic literature search of frugivory and seed dispersal on islands, omitting large, continental islands. This revealed a total of 448 studies, most (75%) published during the last two decades, especially after 2010. Nearly 65% of them were focused on eight archipelagos. There is a paucity of studies in Pacific archipelagos near Asia and Australia, and in the Indian Ocean. Data on island frugivory and seed dispersal are diverse but highly uneven in geographic and conceptual coverage. Despite their limited biodiversity, islands are essential reservoirs of endemic plants and animals and their interactions. Due to the simplicity of insular ecosystems, we can assess the importance of seed dispersal theory and mechanisms at species and community levels. These include the ecological and biogeographical meaning and prevalence of non-standard mechanisms of seed dispersal on islands; the seed dispersal effectiveness and the relative roles of different frugivore guilds (birds and reptiles being the most important); and patterns of community organization and their drivers as revealed by interaction networks. Island systems are characterized by the extinction of many natives and endemics, and high rates of species introductions. Therefore, understanding how these losses and additions alter seed dispersal processes has been a prevailing goal of island studies and an essential foundation for the effective restoration and conservation of islands.

A safe and effective vaccine against COVID-19 is urgently needed in quantities that are sufficient to immunize large populations. Here we report the preclinical development of two vaccine candidates (BNT162b1 and BNT162b2) that contain nucleoside-modified messenger RNA that encodes immunogens derived from the spike glycoprotein (S) of SARS-CoV-2, formulated in lipid nanoparticles. BNT162b1 encodes a soluble, secreted trimerized receptor-binding domain (known as the RBD–foldon). BNT162b2 encodes the full-length transmembrane S glycoprotein, locked in its prefusion conformation by the substitution of two residues with proline (S(K986P/V987P); hereafter, S(P2) (also known as P2 S)). The flexibly tethered RBDs of the RBD–foldon bind to human ACE2 with high avidity. Approximately 20% of the S(P2) trimers are in the two-RBD ‘down’, one-RBD ‘up’ state. In mice, one intramuscular dose of either candidate vaccine elicits a dose-dependent antibody response with high virus-entry inhibition titres and strong T-helper-1 CD4 + and IFNγ + CD8 + T cell responses. Prime–boost vaccination of rhesus macaques ( Macaca mulatta ) with the BNT162b candidates elicits SARS-CoV-2-neutralizing geometric mean titres that are 8.2–18.2× that of a panel of SARS-CoV-2-convalescent human sera. The vaccine candidates protect macaques against challenge with SARS-CoV-2; in particular, BNT162b2 protects the lower respiratory tract against the presence of viral RNA and shows no evidence of disease enhancement. Both candidates are being evaluated in phase I trials in Germany and the USA 1 – 3 , and BNT162b2 is being evaluated in an ongoing global phase II/III trial (NCT04380701 and NCT04368728). BNT162b1 and BNT162b2 are two candidate mRNA vaccines against COVID-19 that elicit high virus-entry inhibition titres in mice, elicit high virus-neutralizing titres in rhesus macaques and protect macaques from SARS-CoV-2 challenge.

Abstract To contain the coronavirus disease 2019 (COVID-19) pandemic, a safe and effective vaccine against the new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is urgently needed in quantities sufficient to immunise large populations. In this study, we report the design, preclinical development, immunogenicity and anti-viral protective effect in rhesus macaques of the BNT162b2 vaccine candidate. BNT162b2 contains an LNP-formulated nucleoside-modified mRNA that encodes the spike glycoprotein captured in its prefusion conformation. After expression of the BNT162b2 coding sequence in cells, approximately 20% of the spike molecules are in the one-RBD ‘up’, two-RBD ‘down’ state. Immunisation of mice with a single dose of BNT162b2 induced dose level-dependent increases in pseudovirus neutralisation titers. Prime-boost vaccination of rhesus macaques elicited authentic SARS-CoV-2 neutralising geometric mean titers 10.2 to 18.0 times that of a SARS-CoV-2 convalescent human serum panel. BNT162b2 generated strong TH1 type CD4+ and IFNγ+ CD8+ T-cell responses in mice and rhesus macaques. The BNT162b2 vaccine candidate fully protected the lungs of immunised rhesus macaques from infectious SARS-CoV-2 challenge. BNT162b2 is currently being evaluated in a global, pivotal Phase 2/3 trial (NCT04368728). Competing Interest Statement U.S. and O.T. are management board members and employees at BioNTech SE (Mainz, Germany); K.C.W., B.G.L., D.S., B.J., T.K. and C.R. are employees at BioNTech SE; A.B.V., A.M., M.V., L.M.K., S.He., A.G., T.Z., A.P., D.E., S.C.D., S.F., S.E., F.B., B.S., A.W., Y.F., H.J., S.A.K., A.P.H., P.A., J.S., C.K., and A.N.K. are employees at BioNTech RNA Pharmaceuticals GmbH (Mainz, Germany); A.B.V., A.M., K.C.W., A.G., S.F., A.N.K and U.S. are inventors on patents and patent applications related to RNA technology and COVID-19 vaccine; A.B.V., A.M., M.V., L.M.K., K.C.W., S.He., B.G.L., A.P., D.E., S.C.D., S.F., S.E., D.S., B.J., B.S., A.P.H., P.A., J.S., C.K., T.K., C.R., A.N.K., O.T. and U.S. have securities from BioNTech SE; I.K., Y.C., K.A.S., J.L., M.M., K.T., M.C.G., S.H., J.A.L.,E.H.M., P.V.S., C.Y.T., D.P., G.S., M.P., I.L.S., T.C., J.O., W.V.K., P.R.D. and K.U.J. are employees of Pfizer and may hold stock options; C.F.-G. and P.-Y.S. received compensation from Pfizer to perform neutralisation assays; J.C., S.H.-U, K.B., R.C., jr., K.J.A. and D.K., are employees of Southwest National Primate Research Center, which received compensation from Pfizer to conduct the animal challenge work; no other relationships or activities that could appear to have influenced the submitted work.

Abstract A safe and effective vaccine against COVID-19 is urgently needed in quantities sufficient to immunise large populations. We report the preclinical development of two BNT162b vaccine candidates, which contain lipid-nanoparticle (LNP) formulated nucleoside-modified mRNA encoding SARS-CoV-2 spike glycoprotein-derived immunogens. BNT162b1 encodes a soluble, secreted, trimerised receptor-binding domain (RBD-foldon). BNT162b2 encodes the full-length transmembrane spike glycoprotein, locked in its prefusion conformation (P2 S). The flexibly tethered RBDs of the RBD-foldon bind ACE2 with high avidity. Approximately 20% of the P 2S trimers are in the two-RBD ‘down,’ one-RBD ‘up’ state. In mice, one intramuscular dose of either candidate elicits a dose-dependent antibody response with high virus-entry inhibition titres and strong TH1 CD4+ and IFNγ+ CD8+ T-cell responses. Prime/boost vaccination of rhesus macaques with BNT162b candidates elicits SARS-CoV-2 neutralising geometric mean titres 8.2 to 18.2 times that of a SARS-CoV-2 convalescent human serum panel. The vaccine candidates protect macaques from SARS-CoV-2 challenge, with BNT162b2 protecting the lower respiratory tract from the presence of viral RNA and with no evidence of disease enhancement. Both candidates are being evaluated in phase 1 trials in Germany and the United States. BNT162b2 is being evaluated in an ongoing global, pivotal Phase 2/3 trial (NCT04380701, NCT04368728). Competing Interest Statement U.S. and O.T. are management board members and employees at BioNTech SE (Mainz, Germany); K.C.W., B.G.L., D.S., B.J., T.H., T.K. and C.R. are employees at BioNTech SE; A.B.V., A.M., M.V., L.M.K., S.H., A.G., T.Z., F.B., A.P., D.E., S.C.D., S.F., S.E., F.B., B.S., A.W., Y.F., H.J., S.A.K., S.S., A.P.H., P.A., J.S., A.A.H.S., C.K., R.d.l.C.G.G., L.F. and A.N.K. are employees at BioNTech RNA Pharmaceuticals GmbH (Mainz, Germany); A.B.V., A.M., K.C.W., A.G., S.F., A.N.K and U.S. are inventors on patents and patent applications related to RNA technology and COVID-19 vaccine; A.B.V., A.M., M.V., L.M.K., K.C.W., S.H., B.G.L., A.P., D.E., S.C.D., S.F., S.E., D.S., B.J., B.S., A.P.H., P.A. J.S., A.A.H.S., T.H., L.F., C.K., T.K., C.R., A.N.K., O.T. and U.S. have securities from BioNTech SE; I.K., Y.C., K.A.S. J.A.L. M.S.M., K.T., A,O.-S., J.A.F., M.C.G., S.H., J.A.L., E.H.M., N.L.N., P.V.S., C.Y.T., D.P., W.V.K., J.O., R.S.S., S,C., T.C., I.L.S., M.W.P., G.S., and P.R.D., K.U.J. are employees of Pfizer and may hold stock options; C.F.-G. and P.-Y.S. received compensation from Pfizer to perform neutralisation assays; M.R.G. received compensation from Pfizer to read and interpret radiographs and CT scans. J.C., S.H.-U, K.B., R.C., Jr., K.J.A. O.G., and D.K., are employees of Southwest National Primate Research Center, which received compensation from Pfizer to conduct the animal challenge work; M.G. is an employee of Texas Biomedical Research Institute, which received compensation from Pfizer to conduct the RT-qPCR viral load quantification; no other relationships or activities that could appear to have influenced the submitted work.