2002). By 12 hours after infection EBV nuclear antigen 2 (EBNA-2) and EBNA leader protein (EBNA-LP) are detected (Alfieri et al. 2001). https://www.cdc.gov/epstein-barr/about-mono.html. 2008). In a follow-up paper from the same group, mice immunized with the tetrameric gp350 showed 4-fold higher titers compared with animals immunized with monomeric gp350 using a virus neutralizing assay (Cui et al. If you care for young children, wash toys that they may have put in their mouths. Accessed Nov. 22, 2022. Direct visualization of antigen-specific CD8 T cells during the primary immune response to Epstein-Barr virus in vivo. Virtually all adult rhesus macaques are naturally infected with rhesus LCV. Subsequent experiments performed in cottontop tamarins showed that purified gp350 in immunostimulating complexes (ISCOMs) or muramyl dipeptide in squalene, recombinant gp350 in alum or muramyl dipeptide in squalene, or adenovirus or vaccinia virus expressing gp350 protected animals from lymphoma after challenge with EBV (reviewed in Cohen 2015). People also are contagious while they have symptoms, which can last from two to four weeks or even longer. 1998, Steven et al. the contents by NLM or the National Institutes of Health. Good handwashing practices are also important and can reduce your risk of infection if you are exposed to the virus. 2015). A potential concern is that patients with who have X-linked lymphoproliferative disease type 1 might not have a normal response to the EBV vaccine. Balfour HH Jr, Odumade OA, Schmeling DO, Mullan BD, Ed JA, Knight JA, Vezina HE, Thomas W, Hogquist KA (2013). Infection with EBV induces antibodies and T cells specific for viral proteins. 2013). There is no vaccine to protect you against mono, and people can spread it before they know they have the illness. Results: EBV is the primary cause of infectious mononucleosis (1, 2).There are ~125,000 new cases of infectious mononucleosis each year in the United States, and it is the most common cause of lost time for new Army recruits (3-5). Glycoproteins, present on the surface of viruses and virus-infected cells, have typically been primary candidates for development of vaccines to prevent infection and/or disease. You can find out more about our use, change your default settings, and withdraw your consent at any time with effect for the future by visiting Cookies Settings, which can also be found in the footer of the site. The best thing you can do to avoid it is to stay away from anyone you know who has it. 2007), but sensitive assays can reliably measure EBV DNA levels in health seropositive persons (Hoshino et al. Although less common, mono can also be spread through sexual contact, blood transfusions, and organ transplants. A rare but serious complication of mono is a ruptured spleen, which can happen if your spleen becomes swollen. CD8+ immunodominance among Epstein-Barr virus lytic cycle antigens directly reflects the efficiency of antigen presentation in lytically infected cells. Epstein-Barr virus and infectious mononucleosis. Phase I/II studies to evaluate safety and immunogenicity of a recombinant gp350 Epstein-Barr virus vaccine in healthy adults. In addition, priorities for future research that were identified included determining disease-predictive surrogate markers of EBV malignancies to use as endpoints for EBV vaccine trials, identifying immune correlates of protection from EBV infection and disease, establishing epidemiologic studies to determine the benefit of an EBV vaccine, development of a plan to determine vaccine efficacy for preventing malignancies, and establishing a strategy to facilitate collaborations between academic, industry, and government organizations to accelerate EBV vaccine development. When you visit the site, Dotdash Meredith and its partners may store or retrieve information on your browser, mostly in the form of cookies. Prospective study of the natural history of infectious mononucleosis caused by Epstein-Barr virus. Front Immunol. Trials of an EBV vaccine to reduce the incidence of Hodgkin lymphoma, multiple sclerosis, or Burkitt lymphoma would be difficult, but feasible. Coghill AE, Bu W, Nguyen H, Hsu WL, Yu KJ, Lou PJ, Wang CP, Chen CJ, Hildesheim A, Cohen JI (2016). government site. To provide you with the most relevant and helpful information, and understand which Rhesus macaques vaccinated with rhesus LCV gp350 had the best level of protection after challenge; animals that still became infected after challenge had the lowest level of rhesus LCV DNA in the blood nearly three years after infection. Cookies collect information about your preferences and your devices and are used to make the site work as you expect it to, to understand how you interact with the site, and to show advertisements that are targeted to your interests. High Epstein-Barr Virus Load and Genomic Diversity Are Associated with Generation of gp350-Specific Neutralizing Antibodies following Acute Infectious Mononucleosis. 2013 Apr 18;31 Suppl 2(0 2):B194-6. Morgan AJ, Mackett M, Finerty S, Arrand JR, Scullion FT, Epstein MA (1988). Accessed Nov. 22, 2022. Heeke DS, Lin R, Rao E, Woo JC, McCarthy MP, Marshall JD (2016). New approaches have recently been developed to express gp350 in a multimeric configuration. There is no vaccine to prevent mono. 2015). Outbreaks are rare. What It Means for You In addition to the infectious disease mononucleosis (mono), the Epstein-Barr virus (EBV) is associated with an increased risk of seven different autoimmune diseases: Systemic lupus erythematosus Rheumatoid arthritis Multiple sclerosis Inflammatory bowel disease Type 1 diabetes Juvenile idiopathic arthritis Celiac disease Immunization of mice with a plasmid expressing gp350 induced antibodies that mediated ADCC and gp350-specific cytotoxic T cells (Jung et al. 2007). All rights reserved. Li W, Duan X, Chen X, Zhan M, Peng H, Meng Y, Li X, Li XY, Pang G, Dou X. The .gov means its official. Cohen JI, Fauci AS, Varmus H, Nabel GJ (2011). Most people who have mononucleosis, also called mono, will have it only once. One month after the third dose of vaccine, 99% of subjects had gp350 antibodies and these antibodies persisted for 18 months; 70% of vaccinated subjects developed competition ELISA antibodies (a surrogate for neutralizing antibody); EBV DNA levels in the blood were not measured. Wedderburn N, Edwards JM, Desgranges C, Fontaine C, Cohen B, de Th G (1984). In sub-Sahara Africa, the incidence of Burkitt lymphoma is 20 per 100,000 in children between the ages of 5 and 9 years old. Prevention Steps Since EBV is transmitted through close contact with others, the best way to prevent infection is by doing the following: Avoid anyone you know who has mono. About 6% of seronegative persons who receive solid organ transplants develop post-transplant lymphoproliferative disease (Sarabu and Hricik, 2016). the unsubscribe link in the e-mail. FOIA Successful treatment of posttransplantation lymphoproliferative disorder (PTLD) following renal allografting is associated with sustained CD8(+) T-cell restoration. Asymptomatic primary Epstein-Barr virus infection occurs in the absence of blood T-cell repertoire perturbations despite high levels of systemic viral load. None of the 10 subjects who received the vaccine developed infectious mononucleosis, while 1 of the 4 placebo recipients developed the disease; 4 of the 10 vaccine recipients developed asymptomatic EBV infection, while 1 of the 4 placebo recipients had an asymptomatic infection. There are about 1,600 known human . information is beneficial, we may combine your email and website usage information with Verywell Health's content is for informational and educational purposes only. How to Prevent the Transmission of Mononucleosis. It is therefore also known as the kissing disease. Mono is common in settings where individuals are in close quarters, such as college dormitories. A novel tetrameric gp350 1470 as a potential Epstein-Barr virus vaccine. The reasons are not entirely clear, but likely include: skepticism about what an EBV vaccine could actually achieve; the impression that infectious mononucleosis is a trivial disease; the lack of . EBV neutralizing antibodies were first reported in rabbits (Thorley-Lawson 1979) and cottontop tamarins (Morgan et al. If you use hand sanitizer, choose one with at least a 60% alcohol content. Initial experiments focused on cottontop tamarins, which develop EBV-positive mono- or oligoclonal B cell large-cell lymphomas after parental inoculation with high titers of virus (Cleary et al. 2003). information highlighted below and resubmit the form. Cui X, Cao Z, Chen Q, Arjunaraja S, Snow AL, Snapper CM (2016). A prior study in which rhesus macaques were vaccinated with a rhesus LCV gp350 vaccine and challenged with wild-type rhesus LCV, showed that animals that became infected after challenge had a lower viral load nearly 3 years after challenge compared with control animals (Sashihara et al. https://www.cdc.gov/epstein-barr/index.html. Click here for an email preview. Moghaddam A, Rosenzweig M, Lee-Parritz D, Annis B, Johnson RP, Wang F (1997). 2003). The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, has launched an early-stage clinical trial to evaluate an investigational preventative vaccine for Epstein-Barr virus (EBV). Xu J, Ahmad A, Blagdon M, DAddario M, Jones JF, Dolcetti R, Vaccher E, Prasad U, Menezes J (1998). Palser AL, Grayson NE, White RE, Corton C, Correia S, Ba Abdullah MM, Watson SJ, Cotten M, Arrand JR, Murray PG, Allday MJ, Rickinson AB, Young LS, Farrell PJ, Kellam P (2015). CD4 T cells recognize immediate-early, early, and late proteins without a preference for the kinetic class of gene expression in EBV seropositive persons (Long et al. Immunization of HLA-A2 transgenic mice with gH peptides induced cytotoxic T cell responses and protected the animals again vaccinia virus expressing gH (Khanna et al. 2022 Dec 2;14(12):2709. doi: 10.3390/v14122709. 1993; Kawaguchi et. 1980; Thorley-Lawson and Poodry, 1982). Primary Immunodeficiencies Associated with EBV Disease. Gu SY, Huang TM, Ruan L, Miao YH, Lu H, Chu CM, Motz M, Wolf H (1995). Mononucleosis. Porcu P, Eisenbeis CF, Pelletier RP, Davies EA, Baiocchi RA, Roychowdhury S, Vourganti S, Nuovo GJ, Marsh WL, Ferketich AK, Henry ML, Ferguson RM, Caligiuri MA (2002). The Journal of Infectious Diseases. These proteins can be detected by CD4 T cells early after infection (Adhikary et al. How long is mono contagious? In: Bowden RA, Ljungman P, Paya CV (eds). While monomeric EBV gp350 was shown in a phase 2 trial to reduce the incidence of infectious mononucleosis, but not the rate of EBV infection, newer formulations of gp350 including multimeric forms, virus-like particles, and nanoparticles may be more effective. As a library, NLM provides access to scientific literature. Mononucleosis, which causes weeks of extreme fatigue, is the most common illness caused by EBV. If you are a Mayo Clinic patient, this could 2016). Woodberry T, Suscovich TJ, Henry LM, Davis JK, Frahm N, Walker BD, Scadden DT, Wang F, Brander C (2005). 1997; Precopio et al. 1985). Book: Mayo Clinic Family Health Book, 5th Edition, Newsletter: Mayo Clinic Health Letter Digital Edition. So, the best prevention is to avoid close contact with someone who may have the disease and to not share items like water bottles, toothbrushes, and eating utensilsanything that can spread salivawith others. Clinical manifestations and treatment of Epstein-Barr virus infection. Early T Cell Recognition of B Cells following Epstein-Barr Virus Infection: Identifying Potential Targets for Prophylactic Vaccination. Precopio ML, Sullivan JL, Willard C, Somasundaran M, Luzuriaga K (2003). 1984). Conclusion: 2016). EBV is associated with lymphoproliferative disease in immunodeficient patients (reviewed in Cohen 2015). Epstein-Barr virus infection. Because Epstein-Barr is an airborne virus, it - as well as mononucleosis - is passed by "droplet spread," Dr . Alternatively these vaccines could induce protective CD4 or CD8 T cell immunity. Hoshino Y, Katano H, Zou P, Hohman P, Marques A, Tyring SK, Follmann D, Cohen JI (2009). B cells neutralizing antibody reaches peak levels at a median of about 180 days after the onset of infectious mononucleosis (Bu et al 2015). Since EBV seronegative recipients of solid organ transplants typically become infected from EBV in the transplanted organ, a vaccine to control proliferation of virus-infected cells in the organ may require T cells in addition to antibody. Co-Infection of the Epstein-Barr Virus and the Kaposi Sarcoma-Associated Herpesvirus. Treatments can ease symptoms until the illness goes away on its own. 1992). Tamarins vaccinated intraperitoneally with purified cell membranes containing gp350, isolated from virus infected (B958) cells, developed neutralizing antibody to EBV and were protected from EBV-tumors after challenge with virus. At present it is unknown which activities mediated by antibodies are most important for protection against EBV infection or disease. The Epstein-Barr virus (EBV) major envelope glycoprotein gp350/220-specific antibody reactivities in the sera of patients with different EBV-associated diseases. Federal government websites often end in .gov or .mil. Callan MF, Tan L, Annels N, Ogg GS, Wilson JD. Infectious mononucleosis, or mono, is a disease spread through saliva and other bodily fluids. Individual tumors of multifocal EB virus-induced malignant lymphomas in tamarins arise from different B-cell clones. . EBV infection of epithelial cells occurs at the cell surface, not through endocytosis. A phase 1 trial using 12.5 ug or 25 ug of EBV gp350 vaccine in alum adjuvant was performed in EBV seronegative children with chronic renal insufficiency while waiting for kidney transplants (Rees et al. CD8 T cell responses during infectious mononucleosis are targeted to EBV lytic antigens including gp350, gH, gL, and gB (reviewed in Taylor et al. Bookshelf EBV glycoprotein gp350 is important for attachment of the virus to B cells. Observations on the EB virus envelope and virus-determined membrane antigen (MA) polypeptides. It's usually caused by the Epstein-Barr virus, but can be caused by other viruses, too. In additional experiments, animals vaccinated with gp350 incorporated into liposomes developed neutralizing antibody and were also protected against challenge with EBV. 2011). 2007), more recent studies show that multiple lytic proteins including BMLF1 (a post-transcriptional regulatory protein), BMRF1 (polymerase-associated processivity factor), BNRF1 (the major tegument protein), BORF1 (DNA packaging protein), BcLF1 (major capsid protein), and BXLF1 (thymidine kinase) are targets of CD4 cells (Long et al. 1999 Feb 26;17(7-8):660-8. doi: 10.1016/s0264-410x(98)00248-5. Sashihara J, Burbelo PD, Savoldo B, Pierson TC, Cohen JI (2009). There is no vaccine to prevent mono. Different types of immunogens to induce T cell responses have been suggested for a prophylactic EBV vaccine (Brooks et al 2016). The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Aalto SM, Juvonen E, Tarkkanen J, Volin L, Haario H, Ruutu T, Hedman K (2007). eCollection 2022. Vaccination of mice with ferritin-gp350 nanoparticles protected the animals from challenge with vaccinia virus expressing gp350; vaccination with encapsulin-gp350 nanoparticles did not protect the mice. infectious mononucleosis an acute infectious disease that causes changes in the leukocytes; it is . sharing sensitive information, make sure youre on a federal A randomized single-blind, placebo-controlled phase 1 study of two doses of an EBV peptide vaccine was tested in HLA B*801 EBV seronegative young adults (Elliott et al. Careers. Mono is a contagious illness that is usually caused by the Epstein-Barr virus. information submitted for this request. Prednisone withdrawal: Why taper down slowly? Vaccine Development for Epstein-Barr Virus. About infectious mononucleosis. They may not know that they have mono, but they can still pass it on to someone else. Emini EA, Schleif WA, Armstrong ME, Silberklang M, Schultz LD, Lehman D, Maigetter RZ, Qualtiere LF, Pearson GR, Ellis RW (1988). Subjects received 5 ug or 50 ug of an EBNA-3A peptide with tetanus toxoid in a water in oil emulsion (Montanide ISA 720) or placebo. High Levels of Antibody that Neutralize B-cell Infection of Epstein-Barr Virus and that Bind EBV gp350 Are Associated with a Lower Risk of Nasopharyngeal Carcinoma. ClinicalTrials.gov identifier: NCT00430534. In another approach, two Newcastle disease virus VLPs were constructed; one containing the ectodomain of EBV gH fused to the Newcastle disease virus F protein, the EBV gL ectodomain fused to the Newcastle disease virus HN protein, and the carboxyl half of EBV EBNA1 fused to the Newcastle disease virus NP protein (Perez et al. Mono has a long incubation period, so it can be difficult to pinpoint when the illness actually started. There is no vaccine for mononucleosis. 2007). A vaccine to reduce EBV post-transplant lymphoproliferative disease would be an important proof of principle to prevent an EBV associated malignancy. (2013) Epstein-Barr Virus. government site. other information we have about you. If you do become sick with mono, you will be able to recover with plenty of rest and fluids. 1991). An EBV vaccine might also be used to prevent X-linked lymphoproliferative disease type 1 in EBV-seronegative boys with mutations in SH2D1A or in other patients with genetic disorders that predispose to EBV malignancies (reviewed in Cohen 2015) who have not yet become infected. About Epstein-Barr virus (EBV). Most cases of mononucleosis are caused by the Epstein-Barr virus (EBV). An official website of the United States government. gp350 is not strictly essential for virus infection, but is important for efficient infection of B cells in vitro (Janz et al. Bu W, Hayes GM, Liu H, Gemmell L, Schmeling DO, Radecki P, Aguilar F, Burbelo PD, Woo J, Balfour HH Jr, Cohen JI (2016). Before EBV BZLF1 encodes the immediate-early protein (Zta). Sore throat, enlarged lymph nodes, and extreme fatigue are common symptoms. It's highly contagious and easily passed from person to person. Methods: Mononucleosis Prevention. Glycoproteins including gp350, gH, gL, gp42, and gB are also recognized by CD4 T cells (reviewed in Taylor et al. You may opt-out of email communications at any time by clicking on One month after receipt of the final dose of gp350 vaccine, 98.7% of subjects showed seroconversion to anti-gp350 antibodies (95% CI, 85.5%-97.9%), and they remained anti-gp350 antibody positive for >18 months. 2014), likely due to pressure to evolve in response to its role as a target for cytotoxic T cells. gp350 is a type I membrane protein and is the most abundant glycoprotein on the surface of virus-infected cells and on virions. Most primary infections with Epstein-Barr virus (EBV) occur in infants or young children and these infections are asymptomatic or result in non-specific symptoms (Cohen 2000). Mice receiving dendritic cells expressing Zta developed Zta-specific T cell responses and had delayed development of EBV lymphoproliferative disease compared with animals receiving dendritic cells not expressing Zta. Swollen spleen (an organ in the upper-left side of the abdomen). But when most people get EBV, they have no symptoms. There is little change in gp350 amino acid sequence in individuals between the time of acute infectious mononucleosis and convalescence; the few changes that do occur are located outside the CR2 binding domain (Weiss et al. Not all potently neutralizing, vaccine-induced antibodies to Epstein-Barr virus ensure protection of susceptible experimental animals. 2011). Drink plenty of water, fruit juice, herbal tea, soup, and broth. 1982). Purification and biologic characterization of a major Epstein Barr virus-induced membrane glycoprotein. T cell responses are important for controlling reactivation of the virus and the level of virus in the blood (reviewed in Taylor et al. Concerning symptoms or worsening symptoms that may warrant a call to your healthcare provider include those that last for more than 10 days and the following: This is not an exhaustive list of symptoms. Epstein-Barr virus: an important vaccine target for cancer prevention. The Epstein-Barr Virus Lytic Protein BZLF1 as a Candidate Target Antigen for Vaccine Development. (1998). Mouse immunized with these EBV VLPs produced neutralizing antibody and T cell responses to viral proteins (Ruiss et al. A total of 181 EBV-seronegative, healthy, young adult volunteers were randomized in a double-blind fashion to receive either placebo or a recombinant EBV subunit glycoprotein 350 (gp350)/aluminum hydroxide and 3-O-desacyl-4'-monophosphoryl lipid A (AS04) candidate vaccine in a 3-dose regimen. 1988; Jackman et al. Comparative immunogenicity studies on Epstein-Barr virus membrane antigen (MA) gp340 with novel adjuvants in mice, rabbits, and cotton-top tamarins. These findings suggest that a vaccine targeting CD8 T cells might focus more on lytic antigens especially immediate-early proteins, while a vaccine targeting CD4 T cells might focus on EBNA-3.