A gB nanoparticle vaccine elicits a protective neutralizing antibody response against EBV.

Epstein-Barr virus (EBV) is a global public health concern, as it is known to cause multiple diseases while also being etiologically associated with a wide range of epithelial and lymphoid malignancies. Currently, there is no available prophylactic vaccine against EBV. gB is the EBV fusion protein that mediates viral membrane fusion and participates in host recognition, making it critical for EBV infection in both B cells and epithelial cells. Here, we present a gB nanoparticle, gB-I53-50 NP, that displays multiple copies of gB. Compared with the gB trimer, gB-I53-50 NP shows improved structural integrity and stability, as well as enhanced immunogenicity in mice and non-human primate (NHP) preclinical models. Immunization and passive transfer demonstrate a robust and durable protective antibody response that protects humanized mice against lethal EBV challenge. This vaccine candidate demonstrates significant potential in preventing EBV infection, providing a possible platform for developing prophylactic vaccines for EBV.

Structure of infective Getah virus at 2.8 Å resolution determined by cryo-electron microscopy.

Getah virus (GETV), a member of the genus alphavirus, is a mosquito-borne pathogen that can cause pyrexia and reproductive losses in animals. Although antibodies to GETV have been found in over 10% of healthy people, there are no reports of clinical symptoms associated with GETV. The biological and pathological properties of GETV are largely unknown and antiviral or vaccine treatments against GETV are still unavailable due to a lack of knowledge of the structure of the GETV virion. Here, we present the structure of infective GETV at a resolution of 2.8 Å with the atomic models of the capsid protein and the envelope glycoproteins E1 and E2. We have identified numerous glycosylation and S-acylation sites in E1 and E2. The surface-exposed glycans indicate a possible impact on viral immune evasion and host cell invasion. The S-acylation sites might be involved in stabilizing the transmembrane assembly of E1 and E2. In addition, a cholesterol and a phospholipid molecule are observed in a transmembrane hydrophobic pocket, together with two more cholesterols surrounding the pocket. The cholesterol and phospholipid stabilize the hydrophobic pocket in the viral envelope membrane. The structural information will assist structure-based antiviral and vaccine screening, design, and optimization.

Evaluating the Association of Clinical Characteristics With Neutralizing Antibody Levels in Patients Who Have Recovered From Mild COVID-19 in Shanghai, China.

Importance: The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) threatens global public health. The association between clinical characteristics of the virus and neutralizing antibodies (NAbs) against this virus have not been well studied. Objective: To examine the association between clinical characteristics and levels of NAbs in patients who recovered from COVID-19. Design, Setting, and Participants: In this cohort study, a total of 175 patients with mild symptoms of COVID-19 who were hospitalized from January 24 to February 26, 2020, were followed up until March 16, 2020, at Shanghai Public Health Clinical Center, Shanghai, China. Exposures: SARS-CoV-2 infections were diagnosed and confirmed by reverse transcriptase-polymerase chain reaction testing of nasopharyngeal samples. Main Outcomes and Measures: The primary outcome was SARS-CoV-2-specific NAb titers. Secondary outcomes included spike-binding antibodies, cross-reactivity against SARS-associated CoV, kinetics of NAb development, and clinical information, including age, sex, disease duration, length of stay, lymphocyte counts, and blood C-reactive protein level. Results: Of the 175 patients with COVID-19, 93 were female (53%); the median age was 50 (interquartile range [IQR], 37-63) years. The median length of hospital stay was 16 (IQR, 13-21) days, and the median disease duration was 22 (IQR, 18-26) days. Variable levels of SARS-CoV-2-specific NAbs were observed at the time of discharge (50% inhibitory dose [ID50], 1076 [IQR, 448-2048]). There were 10 patients whose NAb titers were less than the detectable level of the assay (ID50, <40), and 2 patients who showed very high titers of NAbs, with ID50 levels of 15 989 and 21 567. NAbs were detected in patients from day 4 to 6 and reached peak levels from day 10 to 15 after disease onset. NAbs were unable to cross-react with SARS-associated CoV and NAb titers correlated with the spike-binding antibodies targeting S1 (r = 0.451; 95% CI, 0.320-0.564; P < .001), receptor binding domain (r = 0.484; 95% CI, 0.358-0.592; P < .001), and S2 regions (r = 0.346; 95% CI, 0.204-0.473; P < .001). NAb titers at the time of discharge were significantly higher in the 82 men (1417 [IQR, 541-2253]) than those in the 93 women (905 [IQR, 371-1687]) (median difference, 512; 95% CI, 82-688; P = .01) and at the time of follow-up in 56 male patients (1049 [IQR, 552-2454]) vs 61 female patients (751 [IQR, 216-1301]) (median difference, 298; 95% CI, 86-732; P = .009). Plasma NAb titers were significantly higher in 56 older (1537 [IQR, 877-2427) and 63 middle-aged (1291 [IQR, 504-2126]) patients than in 56 younger patients (459 [IQR, 225-998]) (older vs younger: median difference, 1078; 95% CI, 548-1287; P < .001; middle-aged vs younger: median difference, 832; 95% CI, 284-1013; P < .001). The NAb titers were correlated with plasma C-reactive protein levels (r = 0.508; 95% CI, 0.386-0.614; P < .001) and negatively correlated with lymphocyte counts (r = -0.427; 95% CI, -0.544 to -0.293; P < .001) at the time of admission. Conclusions and Relevance: In this cohort study, among 175 patients who recovered from mild COVID-19 in Shanghai, China, NAb titers to SARS-CoV-2 appeared to vary substantially. Further research is needed to understand the clinical implications of differing NAb titers for protection against future infection.

Isolation and phylogenetic analysis of Getah virus from a commercial modified live vaccine against porcine reproductive and respiratory syndrome virus.

In the present study, Getah virus (GETV) isolate, GETV-V1, was isolated from a commercial PRRSV attenuated live vaccine (MLV), which has been widely used to immunize pigs against porcine reproductive and respiratory syndrome virus (PRRSV). Further analysis demonstrated that nine batches of the PRRSV MLV vaccine (three batches per year from 2017 to 2019) from the same manufacturer were all positive for GETV. Genomic analyses indicated that the GETV-V1 isolate shared the highest sequence identity with the GETV strain, 16-I-674, which was isolated from horses in Japan. The phylogenetic analysis based on the genomic sequences showed that the GETV-V1 strain was clustered with the Japanese GETV strains. Taken together, this is the first report of GETV contamination in live swine vaccines in China. Our findings demonstrate that immunization with commercial live vaccines might be a potential novel route of GETV transmission in swine. This highlights the need for more extensive monitoring of commercial live vaccines.