Multifunctional Pan-ebolavirus Antibody Recognizes a Site of Broad Vulnerability on the Ebolavirus Glycoprotein.

Ebolaviruses cause severe disease in humans, and identification of monoclonal antibodies (mAbs) that are effective against multiple ebolaviruses are important for therapeutics development. Here we describe a distinct class of broadly neutralizing human mAbs with protective capacity against three ebolaviruses infectious for humans: Ebola (EBOV), Sudan (SUDV), and Bundibugyo (BDBV) viruses. We isolated mAbs from human survivors of ebolavirus disease and identified a potent mAb, EBOV-520, which bound to an epitope in the glycoprotein (GP) base region. EBOV-520 efficiently neutralized EBOV, BDBV, and SUDV and also showed protective capacity in relevant animal models of these infections. EBOV-520 mediated protection principally by direct virus neutralization and exhibited multifunctional properties. This study identified a potent naturally occurring mAb and defined key features of the human antibody response that may contribute to broad protection. This multifunctional mAb and related clones are promising candidates for development as broadly protective pan-ebolavirus therapeutic molecules.

Functional SARS-CoV-2 cross-reactive CD4+ T cells established in early childhood decline with age.

Pre-existing SARS-CoV-2-reactive T cells have been identified in SARS-CoV-2-unexposed individuals, potentially modulating COVID-19 and vaccination outcomes. Here, we provide evidence that functional cross-reactive memory CD4+ T cell immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is established in early childhood, mirroring early seroconversion with seasonal human coronavirus OC43. Humoral and cellular immune responses against OC43 and SARS-CoV-2 were assessed in SARS-CoV-2-unexposed children (paired samples at age two and six) and adults (age 26 to 83). Pre-existing SARS-CoV-2-reactive CD4+ T cell responses targeting spike, nucleocapsid, and membrane were closely linked to the frequency of OC43-specific memory CD4+ T cells in childhood. The functional quality of the cross-reactive memory CD4+ T cell responses targeting SARS-CoV-2 spike, but not nucleocapsid, paralleled OC43-specific T cell responses. OC43-specific antibodies were prevalent already at age two. However, they did not increase further with age, contrasting with the antibody magnitudes against HKU1 (ß-coronavirus), 229E and NL63 (α-coronaviruses), rhinovirus, Epstein-Barr virus (EBV), and influenza virus, which increased after age two. The quality of the memory CD4+ T cell responses peaked at age six and subsequently declined with age, with diminished expression of interferon (IFN)-γ, interleukin (IL)-2, tumor necrosis factor (TNF), and CD38 in late adulthood. Age-dependent qualitative differences in the pre-existing SARS-CoV-2-reactive T cell responses may reflect the ability of the host to control coronavirus infections and respond to vaccination.

Changes in Genital HPV Prevalence during 12 Years Girls-Only Bivalent HPV Vaccination: Results from a Biennial Repeated Cross-Sectional Study.

BACKGROUND: From 2009 until 2021, bivalent HPV vaccination was offered only to girls in the Netherlands. We aimed to study the impact of girls-only HPV vaccination on genital HPV prevalence among young adults. METHODS AND FINDINGS: PASSYON is a biennial repeated cross-sectional study (2009-21) among sexual health clinic clients aged 16-24 years old. Questionnaires elicited data on demographics, sexual behaviour and HPV vaccination status. Genital samples were collected and analysed using a PCR-based assay (SPF10-LiPA25). Type-specific prevalence trends of 12 high-risk (hr) genotypes were analysed as the adjusted average annual change (aAAC), estimated using Poisson GEE models. The relation between aAAC and phylogenetic distance to HPV-16/18 was assessed by means of regression and rank correlation analysis. Questionnaires and genital samples were collected from 8,889 females and 3,300 heterosexual males (HM). 4,829 females reported to be unvaccinated (54·3%). Among females (irrespective of vaccination status), prevalences of HPV-16/18/31/33/35/45 decreased significantly over time. Increasing trends were observed for HPV-39/52/56. Among both HM and unvaccinated females HPV-16/18 prevalence significantly declined, as did HPV-31 among HM. In contrast, HPV-52/58 increased significantly among HM and unvaccinated females. The type-specific aAAC correlated well with the phylogenetic distance to HPV-16/18. CONCLUSIONS: During twelve years girls-only bivalent HPV vaccination in the Netherlands, decreasing trends of the vaccine types and cross-protected types were observed among females. Herd protection of vaccine-types was observed for HM and unvaccinated females, and one cross-protected type for HM. Increasing prevalence trends of HPV types with large phylogenetic distance to the vaccine types might indicate type-replacement.

Protection of the receptor binding domain (RBD) dimer against SARS-CoV-2 and its variants.

IMPORTANCE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants achieved immune escape and became less virulent and easily transmissible through rapid mutation in the spike protein, thus the efficacy of vaccines on the market or in development continues to be challenged. Updating the vaccine, exploring compromise vaccination strategies, and evaluating the efficacy of candidate vaccines for the emerging variants in a timely manner are important to combat complex and volatile SARS-CoV-2. This study reports that vaccines prepared from the dimeric receptor-binding domain (RBD) recombinant protein, which can be quickly produced using a mature and stable process platform, had both good immunogenicity and protection in vivo and could completely protect rodents from lethal challenge by SARS-CoV-2 and its variants, including the emerging Omicron XBB.1.16, highlighting the value of dimeric recombinant vaccines in the post-COVID-19 era.

Examining the effectiveness and duration of adjuvanted vs. non-adjuvanted influenza vaccines in protecting older adults against symptomatic SARS-CoV-2 infection.

Annual influenza vaccination is one of the main public health measures able to drastically reduce the burden of this infectious disease. Some evidence suggests 'trained immunity' triggered by influenza vaccine might reduce the risk of SARS-CoV-2 infection. Adjuvanted influenza vaccines are known to induce a broader cross-reactive immunity. No studies investigated the effect of adjuvanted vs. non-adjuvanted influenza vaccines on the risk of symptomatic SARS-CoV-2 infection. A case-control analysis nested in a cohort of subjects aged ≥65 years and immunized with adjuvanted or non-adjuvanted influenza vaccines was conducted. Although no statistically significant (OR = 0.87; P = .082) difference between the two vaccine types was observed for the 9-month follow-up period, a 17% (OR = 0.83; P = .042) reduction in the odds of COVID-19 was observed for adjuvanted vaccines with a 6-month follow-up. Further evidence is needed, but these results might have implications given the complexity of the upcoming winter seasons, in which the co-occurrence of influenza, SARS-CoV-2 and other respiratory infections (e.g., syncytial virus) might be unpredictable.

A chimeric porcine reproductive and respiratory syndrome virus 1 strain containing synthetic ORF2-6 genes can trigger T follicular helper cell and heterologous neutralizing antibody responses and confer enhanced cross-protection.

The prevalence of porcine reproductive and respiratory syndrome virus 1 (PRRSV1) isolates has continued to increase in Chinese swine herds in recent years. However, no effective control strategy is available for PRRSV1 infection in China. In this study, we generated the first infectious cDNA clone (rHLJB1) of a Chinese PRRSV1 isolate and subsequently used it as a backbone to construct an ORF2-6 chimeric virus (ORF2-6-CON). This virus contained a synthesized consensus sequence of the PRRSV1 ORF2-6 gene encoding all the envelope proteins. The ORF2-6 consensus sequence shared > 90% nucleotide similarity with four representative strains (Amervac, BJEU06-1, HKEU16 and NMEU09-1) of PRRSV1 in China. ORF2-6-CON had replication efficacy similar to that of the backbone rHLJB1 virus in primary alveolar macrophages (PAMs) and exhibited cell tropism in Marc-145 cells. Piglet inoculation and challenge studies indicated that ORF2-6-CON is not pathogenic to piglets and can induce enhanced cross-protection against a heterologous SD1291 isolate. Notably, ORF2-6-CON inoculation induced higher levels of heterologous neutralizing antibodies (nAbs) against SD1291 than rHLJB1 inoculation, which was concurrent with a higher percentage of T follicular helper (Tfh) cells in tracheobronchial lymph nodes (TBLNs), providing the first clue that porcine Tfh cells are correlated with heterologous PRRSV nAb responses. The number of SD1291-strain-specific IFNγ-secreting cells was similar in ORF2-6-CON-inoculated and rHLJB1-inoculated pigs. Overall, our findings support that the Marc-145-adapted ORF2-6-CON can trigger Tfh cell and heterologous nAb responses to confer improved cross-protection and may serve as a candidate strain for the development of a cross-protective PRRSV1 vaccine.

Evaluating the cost-effectiveness of HPV vaccination for adolescent girls in Japan: A comparison of 2-valent, 4-valent, and 9-valent HPV vaccines with consideration of cross-protection.

OBJECTIVE: In April 2023, the Japanese Health Ministry panel approved the inclusion of the 9-valent human papillomavirus (9vHPV) vaccine in the National Immunization Program, alongside the 2-valent (2vHPV) and 4-valent HPV (4vHPV) vaccines. In response to this, we evaluated the cost-effectiveness of these three vaccines for routine immunization of girls aged 12-16 in Japan, considering the cross-protection of 2vHPV and 4vHPV vaccines. METHODS: We constructed an age-structured mathematical model for HPV transmission, aiming to quantify the economic and epidemiological effects of various HPV vaccination strategies over a 70-year period in Japan. We determined incremental costs and quality-adjusted life years (QALYs) for each strategy, applying a 3% annual discount. Univariate and probabilistic sensitivity analyses were conducted to assess the uncertainty of our model results, with all evaluations done in 2023. RESULTS: Our projections indicate that the HPV vaccination program in Japan will significantly reduce the incidence of HPV-related diseases. All HPV vaccination strategies, using the 2vHPV, 4vHPV, and 9vHPV vaccines, were found to be cost-effective compared to no vaccination, with incremental cost-effectiveness ratios of ¥971,447/QALY, ¥1,237,297/QALY, and ¥742,084/QALY, respectively. Direct comparisons between vaccines demonstrated that the 9vHPV vaccination was more cost-effective than the 2vHPV vaccination, whereas 4vHPV vaccination was dominated by 2vHPV vaccination. CONCLUSIONS: Our study validates the cost-effectiveness of implementing the 9vHPV vaccine as the primary option over the 2vHPV or 4vHPV vaccine for girls in Japan. These findings underscore the need to improve the acceptance rate and coverage of HPV vaccinations in the country.

Antigenic similarities and clinical cross-protection between variant and classic non-viscous strains of Moritella viscosa in Atlantic salmon in Norway.

Moritella viscosa (M. viscosa) is one of the major etiological agents of winter-ulcers in Atlantic salmon (Salmo salar) in Norway. Outbreaks of ulcerative disease in farmed fish occur across the North Atlantic region, causing reduced animal welfare and economical challenges, and are of hindrance for sustainable growth within the industry. Commercially available multivalent core vaccines containing inactivated bacterin of M. viscosa reduce mortality and clinical signs related to winter ulcer disease. It has previously been described two major genetic clades within M. viscosa, typical (hereafter referred to as classic) and variant, based on gyrB sequencing. In addition, there are phenotypical traits such as viscosity that may differ between different types of isolates. Western blot using salmon plasma showed that classic non-viscous strains are antigenically different from the classic viscous type included in core vaccines. Further, Western blot also showed that there are similarities in binding patterns between Norwegian variant and classic non-viscous isolates, indicating they may be antigenically related. Vaccination-challenge trials using Norwegian gyrB-classic non-viscous isolates of M. viscosa, demonstrate that the isolates from the classic clade that are included in current commercial multivalent core vaccines, provide limited cross protection against the emerging non-viscous strains. However, a vaccine recently approved for marketing authorization in Norway, containing inactivated antigen of a variant M. viscosa strain, demonstrates reduced mortality as well as clinical signs caused by infections with the classic non-viscous M. viscosa isolated from outbreaks in Norwegian salmon farms. The study shows that there are antigenic similarities between variant and classic non-viscous types of M. viscosa, and these similarities are mirrored in the observed cross-protection in vaccination-challenge trials.

Characterization of Streptococcus agalactiae 1a isolated from farmed Nile tilapia (Oreochromis niloticus) in North America, Central America, and Southeast Asia.

Streptococcosis caused by Streptococcus agalactiae 1a in Nile tilapia (Oreochromis niloticus) is a severe disease challenge for the global supply of tilapia. Currently, the extensive use of antibiotics is the primary curative tool used to minimize the impact of the disease. Vaccination is a prophylactic measure that has been shown to reduce antibiotic use in the aquaculture sector substantially. However, no commercially licensed vaccine against Streptococcus agalactiae 1a is currently available. This study aimed to investigate, through molecular and immunological methods, if Streptococcus agalactiae 1a isolates collected from North America (NAM), Central America (CAM), and Southeast Asia (SEA) were similarly suitable for the development of a potentially effective vaccine to serve the global tilapia farming industry. Our comparative data showed that the Streptococcus agalactiae 1a isolates from NAM, CAM and SEA had similar biochemical profiles, and genetic multi-locus sequence typing (MLST) analysis showed that the NAM and CAM isolates belonged to sequence type 7 (ST-7) and clonal complex 1, while isolates from SEA grouped into three sequence types (ST-1650, ST-500, and ST-7) and two distinct clonal complexes (CC1 and CC12). Isolates from NAM, CAM, and SEA displayed similar antigenic profiles determined by western blotting with polyclonal rabbit antisera, which was supported by in vivo cross-protection studies, showing that fish immunized with vaccines based on SEA and CAM isolates with different genetic MLST profiles were highly protected against cross-challenge using the same bacterial strains for challenge. Overall, the data obtained from our investigations provide strong indications that Streptococcus agalactiae 1a distributed in NAM, CAM, and SEA are serologically uniform pathogens, and vaccines based on isolates of Streptococcus agalactiae 1a from these regions may be suited for vaccination of tilapia worldwide.

Oral vaccination of young broilers with a live Salmonella Typhimurium vaccine reduces caecal and internal organ colonization following a Salmonella Infantis challenge in a seeder-bird model.

Poultry products are an important source of foodborne Salmonella infections in humans. Amongst these, the prevalence of S. Infantis is rising. In this study, the protection efficacy of an authorized live-attenuated S. Typhimurium vaccine against S. Infantis, was examined using a seeder-bird model in broilers. Vaccinated birds displayed a significantly lower colonization of S. Infantis bacteria in the caeca compared to the non-vaccinated counterparts (P = 0.017), with no significant differences observed in the spleen among the groups, three days post-infection. Thirty-two days post-infection, the disparity in average S. Infantis concentration between all-vaccinated and non-vaccinated birds was significant in both caeca (P = 0.0003) and spleen (P = 0.0002). Interestingly, a third group, consisting of seeder birds that were not vaccinated but housed with vaccinated penmates, exhibited significantly lower S. Infantis levels in both caeca (P = 0.0014) and spleen (P < 0.0001) compared to the non-vaccinated group. These findings underscore the potential of a live-attenuated S. Typhimurium vaccine administered to 2-day-old chicks in conferring protection against S. Infantis in broilers up to slaughter age.

Molecular approaches for the management of papaya ringspot virus infecting papaya: a comprehensive review.

Papaya ringspot virus (PRSV) is a catastrophic disease that causes huge yield losses in papaya cultivation around the world. Yield losses in severely infected plants can be upto 100%. Because of this disease, papaya cultivation has been shifted to other crops in some areas of the world. Many conventional methods and breeding approaches are used against this disease, which turns out to be less effective. Considering the yield loss caused by PRSV in papaya, it is high time to focus on alternative control methods. To implement effective management strategies, molecular approaches such as Marker Assisted Breeding (MAS) or transgenic methods involving post-transcriptional gene silencing targeting the genome viz., coat protein, replicase gene, or HC Pro can be pursued. However, the public's reluctance to widely accept the transgenic approach due to health and environmental concerns necessitates a consideration of non-transgenic alternatives. Prioritizing safety and ensuring efficient virus control, non-transgenic approaches which encompass cross-protection, genome editing, and topical applications of dsRNA to induce gene silencing within the host, can be adopted. This review aims to provide comprehensive insights of various molecular tools used in managing PRSV which in turn will help in sustainable agriculture.

Molecular Virology of Orthopoxviruses with Special Reference to Monkeypox Virus.

Poxviruses are large (200-450 nm) and enveloped viruses carrying double-stranded DNA genome with an epidermal cell-specific adaptation. The genus Orthopoxvirus within Poxviridae family constitutes several medically and veterinary important viruses including variola (smallpox), vaccinia, monkeypox virus (MPXV), and cowpox. The monkeypox disease (mpox) has recently emerged as a public health emergency caused by MPXV. An increasing number of human cases of MPXV have been documented in non-endemic nations without any known history of contact with animals brought in from endemic and enzootic regions, nor have they involved travel to an area where the virus was typically prevalent. Here, we review the MPXV replication, virus pathobiology, mechanism of viral infection transmission, virus evasion the host innate immunity and antiviral therapies against Mpox. Moreover, preventive measures including vaccination were discussed and concluded that cross-protection against MPXV may be possible using antibodies that are directed against an Orthopoxvirus. Despite the lack of a specialised antiviral medication, several compounds such as Cidofovir and Ribavirin warrant consideration against mpox.

How immunity from and interaction with seasonal coronaviruses can shape SARS-CoV-2 epidemiology.

We hypothesized that cross-protection from seasonal epidemics of human coronaviruses (HCoVs) could have affected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, including generating reduced susceptibility in children. To determine what the prepandemic distribution of immunity to HCoVs was, we fitted a mathematical model to 6 y of seasonal coronavirus surveillance data from England and Wales. We estimated a duration of immunity to seasonal HCoVs of 7.8 y (95% CI 6.3 to 8.1) and show that, while cross-protection between HCoV and SARS-CoV-2 may contribute to the age distribution, it is insufficient to explain the age pattern of SARS-CoV-2 infections in the first wave of the pandemic in England and Wales. Projections from our model illustrate how different strengths of cross-protection between circulating coronaviruses could determine the frequency and magnitude of SARS-CoV-2 epidemics over the coming decade, as well as the potential impact of cross-protection on future seasonal coronavirus transmission.

Conservation of HLA Spike Protein Epitopes Supports T Cell Cross-Protection in SARS-CoV-2 Vaccinated Individuals against the Potentially Zoonotic Coronavirus Khosta-2.

Heterologous vaccines, which induce immunity against several related pathogens, can be a very useful and rapid way to deal with new pandemics. In this study, the potential impact of licensed COVID-19 vaccines on cytotoxic and helper cell immune responses against Khosta-2, a novel sarbecovirus that productively infects human cells, was analyzed for the 567 and 41 most common HLA class I and II alleles, respectively. Computational predictions indicated that most of these 608 alleles, covering more than 90% of the human population, contain sufficient fully conserved T-cell epitopes between the Khosta-2 and SARS-CoV-2 spike-in proteins. Ninety percent of these fully conserved peptides for class I and 93% for class II HLA molecules were verified as epitopes recognized by CD8+ or CD4+ T lymphocytes, respectively. These results show a very high correlation between bioinformatic prediction and experimental assays, which strongly validates this study. This immunoinformatics analysis allowed a broader assessment of the alleles that recognize these peptides, a global approach at the population level that is not possible with experimental assays. In summary, these findings suggest that both cytotoxic and helper cell immune protection elicited by currently licensed COVID-19 vaccines should be effective against Khosta-2 virus infection. Finally, by being rapidly adaptable to future coronavirus pandemics, this study has potential public health implications.

Preexisting Immunity Does Not Prevent Efficacy of Vesicular Stomatitis Virus-Based Filovirus Vaccines in Nonhuman Primates.

Ebola virus (EBOV) and Marburg virus (MARV) made headlines in the past decade, causing outbreaks of human disease in previously nonendemic yet overlapping areas. While EBOV outbreaks can be mitigated with licensed vaccines and treatments, there is not yet a licensed countermeasure for MARV. Here, we used nonhuman primates (NHPs) previously vaccinated with vesicular stomatitis virus (VSV)-MARV and protected against lethal MARV challenge. After a resting period of 9 months, these NHPs were revaccinated with VSV-EBOV and challenged with EBOV, resulting in 75% survival. Surviving NHPs developed EBOV glycoprotein (GP)-specific antibody titers and no viremia or clinical signs of disease. The single vaccinated NHP succumbing to challenge showed the lowest EBOV GP-specific antibody response after challenge, supporting previous findings with VSV-EBOV that antigen-specific antibodies are critical in mediating protection. This study again demonstrates that VSVΔG-based filovirus vaccine can be successfully used in individuals with preexisting VSV vector immunity, highlighting the platform's applicability for consecutive outbreak response.

A broadly immunogenic polyvalent Shigella multiepitope fusion antigen protein protects against Shigella sonnei and Shigella flexneri lethal pulmonary challenges in mice.

There are no licensed vaccines for Shigella, a leading cause of children's diarrhea and a common etiology of travelers' diarrhea. To develop a cross-protective Shigella vaccine, in this study, we constructed a polyvalent protein immunogen to present conserved immunodominant epitopes of Shigella invasion plasmid antigens B (IpaB) and D (IpaD), VirG, GuaB, and Shiga toxins on backbone protein IpaD, by applying an epitope- and structure-based multiepitope-fusion-antigen (MEFA) vaccinology platform, examined protein (Shigella MEFA) broad immunogenicity, and evaluated antibody function against Shigella invasion and Shiga toxin cytotoxicity but also protection against Shigella lethal challenge. Mice intramuscularly immunized with Shigella MEFA protein developed IgG responses to IpaB, IpaD, VirG, GuaB, and Shiga toxins 1 and 2; mouse sera significantly reduced invasion of Shigella sonnei, Shigella flexneri serotype 2a, 3a, or 6, Shigella boydii, and Shigella dysenteriae type 1 and neutralized cytotoxicity of Shiga toxins of Shigella and Shiga toxin-producing Escherichia coli in vitro. Moreover, mice intranasally immunized with Shigella MEFA protein (adjuvanted with dmLT) developed antigen-specific serum IgG, lung IgG and IgA, and fecal IgA antibodies, and survived from lethal pulmonary challenge with S. sonnei or S. flexneri serotype 2a, 3a, or 6. In contrast, the control mice died, became unresponsive, or lost 20% of body weight in 48 h. These results indicated that this Shigella MEFA protein is broadly immunogenic, induces broadly functional antibodies, and cross-protects against lethal pulmonary challenges with S. sonnei or S. flexneri serotypes, suggesting a potential application of this polyvalent MEFA protein in Shigella vaccine development.

Generation of Attenuated Mutants of East Asian Passiflora Virus for Disease Management by Cross Protection.

East Asian passiflora virus (EAPV) seriously affects passionfruit production in Taiwan and Vietnam. In this study, an infectious clone of the EAPV Taiwan strain (EAPV-TW) was constructed, and EAPV-TWnss, with an nss tag attached to its helper component-protease (HC-Pro), was generated for monitoring the virus. Four conserved motifs of EAPV-TW HC-Pro were manipulated to create single mutations of F8I (simplified as I8), R181I (I181), F206L (L206), and E397N (N397) and double mutations of I8I181, I8L206, I8N397, I181L206, I181N397, and L206N397. Four mutants, EAPV I8I181, I8N397, I181L206, and I181N397, infected Nicotiana benthamiana and yellow passionfruit plants without conspicuous symptoms. Mutants EAPV I181N397 and I8N397 were stable after six passages in yellow passionfruit plants and expressed a zigzag pattern of accumulation dynamic, typical of beneficial protective viruses. An agroinfiltration assay indicated that the RNA silencing suppression capabilities of the four double mutated HC-Pros are significantly reduced. Mutant EAPV I181N397 accumulated the highest level of the small interfering RNA at 10 days postinoculation (dpi) in N. benthamiana plants, then dropped to background levels after 15 dpi. In both N. benthamiana and yellow passionfruit plants, EAPV I181N397 conferred complete cross protection (100%) against severe EAPV-TWnss, as defined by no severe symptoms and absence of the challenge virus, checked by Western blotting and reverse transcription PCR. Mutant EAPV I8N397 provided high degrees of complete protection against EAPV-TWnss in yellow passionfruit plants (90%) but not in N. benthamiana plants (0%). Both mutants showed complete protection (100%) against the Vietnam severe strain EAPV-GL1 in passionfruit plants. Thus, the mutants EAPV I181N397 and I8N397 have excellent potential for controlling EAPV in Taiwan and Vietnam. [Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Inactivated SARS-CoV-2 Vaccine Shows Cross-Protection against Bat SARS-Related Coronaviruses in Human ACE2 Transgenic Mice.

Severe acute respiratory syndrome coronavirus (SARS-CoV-1) and SARS-CoV-2 are highly pathogenic to humans and have caused pandemics in 2003 and 2019, respectively. Genetically diverse SARS-related coronaviruses (SARSr-CoVs) have been detected or isolated from bats, and some of these viruses have been demonstrated to utilize human angiotensin-converting enzyme 2 (ACE2) as a receptor and to have the potential to spill over to humans. A pan-sarbecovirus vaccine that provides protection against SARSr-CoV infection is urgently needed. In this study, we evaluated the protective efficacy of an inactivated SARS-CoV-2 vaccine against recombinant SARSr-CoVs carrying two different spike proteins (named rWIV1 and rRsSHC014S, respectively). Although serum neutralizing assays showed limited cross-reactivity between the three viruses, the inactivated SARS-CoV-2 vaccine provided full protection against SARS-CoV-2 and rWIV1 and partial protection against rRsSHC014S infection in human ACE2 transgenic mice. Passive transfer of SARS-CoV-2-vaccinated mouse sera provided low protection for rWIV1 but not for rRsSHC014S infection in human ACE2 mice. A specific cellular immune response induced by WIV1 membrane protein peptides was detected in the vaccinated animals, which may explain the cross-protection of the inactivated vaccine. This study shows the possibility of developing a pan-sarbecovirus vaccine against SARSr-CoVs for future preparedness. IMPORTANCE The genetic diversity of SARSr-CoVs in wildlife and their potential risk of cross-species infection highlight the necessity of developing wide-spectrum vaccines against infection of various SARSr-CoVs. In this study, we tested the protective efficacy of the SARS-CoV-2 inactivated vaccine (IAV) against two SARSr-CoVs with different spike proteins in human ACE2 transgenic mice. We demonstrate that the SARS-CoV-2 IAV provides full protection against rWIV1 and partial protection against rRsSHC014S. The T-cell response stimulated by the M protein may account for the cross protection against heterogeneous SARSr-CoVs. Our findings suggest the feasibility of the development of pan-sarbecovirus vaccines, which can be a strategy of preparedness for future outbreaks caused by novel SARSr-CoVs from wildlife.

Investigating the interactions of endornaviruses with each other and with other viruses in common bean, Phaseolus vulgaris.

BACKGROUND: Plant viruses of the genus Alphaendornavirus are transmitted solely via seed and pollen and generally cause no apparent disease. It has been conjectured that certain plant endornaviruses may confer advantages on their hosts through improved performance (e.g., seed yield) or resilience to abiotic or biotic insult. We recently characterised nine common bean (Phaseolus vulgaris L.) varieties that harboured either Phaseolus vulgaris endornavirus (PvEV1) alone, or PvEV1 in combination with PvEV2 or PvEV1 in combination with PvEV2 and PvEV3. Here, we investigated the interactions of these endornaviruses with each other, and with three infectious pathogenic viruses: cucumber mosaic virus (CMV), bean common mosaic virus (BCMV), and bean common mosaic necrosis virus (BCMNV). RESULTS: In lines harbouring PvEV1, PvEV1 and PvEV2, or PvEV1, PvEV2 plus PvEV3, the levels of PvEV1 and PvEV3 RNA were very similar between lines, although there were variations in PvEV2 RNA accumulation. In plants inoculated with infectious viruses, CMV, BCMV and BCMNV levels varied between lines, but this was most likely due to host genotype differences rather than to the presence or absence of endornaviruses. We tested the effects of endornaviruses on seed production and seedborne transmission of infectious pathogenic viruses but found no consistent relationship between the presence of endornaviruses and seed yield or protection from seedborne transmission of infectious pathogenic viruses. CONCLUSIONS: It was concluded that endornaviruses do not interfere with each other's accumulation. There appears to be no direct synergy or competition between infectious pathogenic viruses and endornaviruses, however, the effects of host genotype may obscure interactions between endornaviruses and infectious viruses. There is no consistent effect of endornaviruses on seed yield or susceptibility to seedborne transmission of other viruses.

VLPs containing stalk domain and ectodomain of matrix protein 2 of influenza induce protection in mice.

BACKGROUND: As a result of antigenic drift, current influenza vaccines provide limited protection against circulating influenza viruses, and vaccines with broad cross protection are urgently needed. Hemagglutinin stalk domain and ectodomain of matrix protein 2 are highly conserved among influenza viruses and have great potential for use as a universal vaccine. METHODS: In this study, we co-expressed the stalk domain and M2e on the surface of cell membranes and generated chimeric and standard virus-like particles of influenza to improve antigen immunogenicity. We subsequently immunized BALB/c mice through intranasal and intramuscular routes. RESULTS: Data obtained demonstrated that vaccination with VLPs elicited high levels of serum-specific IgG (approximately 30-fold higher than that obtained with soluble protein), induced increased ADCC activity to the influenza virus, and enhanced T cell as well as mucosal immune responses. Furthermore, mice immunized by VLP had elevated level of mucosal HA and 4M2e specific IgA titers and cytokine production as compared to mice immunized with soluble protein. Additionally, the VLP-immunized group exhibited long-lasting humoral antibody responses and effectively reduced lung viral titers after the challenge. Compared to the 4M2e-VLP and mHA-VLP groups, the chimeric VLP group experienced cross-protection against the lethal challenge with homologous and heterologous viruses. The stalk domain specific antibody conferred better protection than the 4M2e specific antibody. CONCLUSION: Our findings demonstrated that the chimeric VLPs anchored with the stalk domain and M2e showed efficacy in reducing viral loads after the influenza virus challenge in the mice model. This antibody can be used in humans to broadly protect against a variety of influenza virus subtypes. The chimeric VLPs represent a novel approach to increase antigen immunogenicity and are promising candidates for a universal influenza vaccine.