Antibodies to the hemagglutinin (HA) and neuraminidase (NA) glycoproteins are the major mediators of protection against influenza virus infection. Here, we report that current influenza vaccines poorly display key NA epitopes and rarely induce NA-reactive B cells. Conversely, influenza virus infection induces NA-reactive B cells at a frequency that approaches (H1N1) or exceeds (H3N2) that of HA-reactive B cells. NA-reactive antibodies display broad binding activity spanning the entire history of influenza A virus circulation in humans, including the original pandemic strains of both H1N1 and H3N2 subtypes. The antibodies robustly inhibit the enzymatic activity of NA, including oseltamivir-resistant variants, and provide robust prophylactic protection, including against avian H5N1 viruses, in vivo. When used therapeutically, NA-reactive antibodies protected mice from lethal influenza virus challenge even 48 hr post infection. These findings strongly suggest that influenza vaccines should be optimized to improve targeting of NA for durable and broad protection against divergent influenza strains.

An emerging respiratory infectious disease with high mortality, Middle East respiratory syndrome (MERS), is caused by a novel coronavirus (MERS-CoV). It was first reported in 2012 in Saudi Arabia and has now spread to eight countries. Development of effective therapeutics and vaccines is crucial to save lives and halt the spread of MERS-CoV. Here, we show that a recombinant protein containing a 212-amino acid fragment (residues 377-588) in the truncated receptor-binding domain (RBD: residues 367–606) of MERS-CoV spike (S) protein fused with human IgG Fc fragment (S377-588-Fc) is highly expressed in the culture supernatant of transfected 293T cells. The purified S377-588-Fc protein efficiently binds to dipeptidyl peptidase 4 (DPP4), the receptor of MERS-CoV, and potently inhibited MERS-CoV infection, suggesting its potential to be further developed as a therapeutic modality for treating MERS-CoV infection and saving the patients’ lives. The recombinant S377-588-Fc is able to induce in the vaccinated mice strong MERS-CoV S-specific antibodies, which blocks the binding of RBD to DPP4 receptor and effectively neutralizes MERS-CoV infection. These findings indicate that this truncated RBD protein shows promise for further development as an effective and safe vaccine for the prevention of MERS-CoV infection.

Background Influenza viruses cause substantial annual morbidity and mortality globally. Current vaccines protect against influenza only when well matched to the circulating strains. However, antigenic drift can cause considerable mismatches between vaccine and circulating strains, substantially reducing vaccine effectiveness. Moreover, current seasonal vaccines are ineffective against pandemic influenza, and production of a vaccine matched to a newly emerging virus strain takes months. Therefore, there is an unmet medical need for a broadly protective influenza virus vaccine. We aimed to test the ability of chimeric H1 haemagglutinin-based universal influenza virus vaccine candidates to induce broadly cross-reactive antibodies targeting the stalk domain of group 1 haemagglutininexpressing influenza viruses. Methods We did a randomised, observer-blinded, phase 1 study in healthy adults in two centres in the USA. Participants were randomly assigned to one of three prime-boost, chimeric haemagglutinin-based vaccine regimens or one of two placebo groups. The vaccine regimens included a chimeric H8/1, intranasal, live-attenuated vaccine on day 1 followed by a non-adjuvanted, chimeric H5/1, intramuscular, inactivated vaccine on day 85; the same regimen but with the inactivated vaccine being adjuvanted with AS03; and an AS03-adjuvanted, chimeric H8/1, intramuscular, inactivated vaccine followed by an AS03-adjuvanted, chimeric H5/1, intramuscular, inactivated vaccine. In this planned interim analysis, the primary endpoints of reactogenicity and safety were assessed by blinded study group. We also assessed anti-H1 haemagglutinin stalk, anti-H2, anti-H9, and anti-H18 IgG antibody titres and plasmablast and memory B-cell responses in peripheral blood. This trial is registered with ClinicalTrials.gov, number NCT03300050.

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The newly emerged Middle East respiratory syndrome coronavirus (MERS-CoV) has infected at least 77 people, with a fatality rate of more than 50%. Alarmingly, the virus demonstrates the capability of human-to-human transmission, raising the possibility of global spread and endangering world health and economy. Here we have identified the receptor-binding domain (RBD) from the MERS-CoV spike protein and determined its crystal structure. This study also presents a structural comparison of MERS-CoV RBD with other coronavirus RBDs, successfully positioning MERS-CoV on the landscape of coronavirus evolution and providing insights into receptor binding by MERS-CoV. Furthermore, we found that MERS-CoV RBD functions as an effective entry inhibitor of MERS-CoV. The identified MERS-CoV RBD may also serve as a potential candidate for MERS-CoV subunit vaccines. Overall, this study enhances our understanding of the evolution of coronavirus RBDs, provides insights into receptor recognition by MERS-CoV, and may help control the transmission of MERS-CoV in humans. Since the summer of 2012, a novel coronavirus, Middle East respiratory syndrome coronavirus (MERS-CoV), has emerged from the Middle East and spread to parts of Europe. MERS-CoV infection often leads to acute pneumonia and renal failure, and the human fatality rate is more than 50% (1, 2). To date, MERS-CoV has infected at least 77 people and was able to be transmitted from human to human. The genomic sequence of MERS-CoV is closely related to the sequences of certain bat coronaviruses (3-5), raising concerns over persistent bat-to-human cross-species transmission of the virus. The clinical signs and epidemic patterns of MERS-CoV are reminiscent of the severe acute respiratory syndrome coronavirus (SARS-CoV), the etiological agent of the worldwide SARS epidemic in 2002-2003 that infected more than 8,000 people with a ϳ10% fatality rate (6, 7). MERS-CoV poses a significant threat to global health and economy.Coronaviruses are enveloped and positive-stranded RNA viruses and can be divided into three major genera, ␣, ␤, and ␥ (8). They mainly cause respiratory, gastrointestinal, and central nervous system diseases in mammals and birds. Coronaviruses recognize a variety of host receptors. Human NL63 respiratory coronavirus (HCoV-NL63) from ␣-genus and SARS-CoV from ␤-genus both recognize angiotensin-converting enzyme 2 (ACE2) as their host receptor (9, 10). Porcine respiratory coronavirus (PRCV) and some other coronaviruses from ␣-genus recognize aminopeptidase N (APN) (11, 12). Mouse hepatitis coronavirus (MHV) from ␤-genus recognizes carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) (13, 14), although certain MHV strains also recognize heparan sulfate (15, 16). Some coronaviruses from each of the three genera recognize sugars (17-20). MERS-CoV belongs to the ␤-genus and uses human dipeptidyl peptidase 4 (DPP4) as its host receptor (21). Receptor recognition is a major determinant of coronavirus host range and tropism.An envelope-anchored trimeric spike p...