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SAN DIEGO – Although most adults have been exposed, it is very rare to find MS in an individual with no prior EBV exposure.
That apparent relationship has driven interest in a vaccine against EBV in an effort to reduce MS incidence on a population level.
At a session at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS), two researchers debated the potential benefits and pitfalls of such a program. The issues included the possible benefit in MS and other EBV-related conditions such as mononucleosis and various cancers, and whether EBV infection is a sufficient cause for MS, as well as concerns about vaccinating a healthy at-risk population.
Reducing the risk of MS by targeting EBV
Jeffrey I. Cohen, MD, spoke first, and cited several lines of evidence supporting the importance of EBV in MS. One study showed a 32-fold increased risk of MS following primary infection with EBV, and another showed that higher EBV nuclear antigen (EBNA) antibody titers were associated with a 36-fold higher risk of MS. “So we have two completely independent studies suggesting that EBV is really very important as a cofactor for development of MS,” said Dr. Cohen, chief of the laboratory of infectious diseases and chief of the medical virology section at the National Institutes of Health, Bethesda, Md.
EBV is also latent in B cells, and anti-B cell therapy is an effective therapeutic strategy for MS. However, the mechanism remains unknown.
Targeting EBV could involve attacking infected cells, or a therapeutic vaccine could be employed to treat EVB-infected individuals, similar to the shingles vaccine. “In all of these methods, one would end up with fewer EBV infected B cells and as a result, presumably you’d have reduced antigenic stimulation of EBV-infected B cells to stimulate either antibodies or T cells that could damage the nervous system. By reducing this, one might be able to [treat] multiple sclerosis,” said Dr. Cohen.
He did acknowledge concerns. It isn’t yet understood whether destroying EBV-infected cells would actually improve outcomes. It also may be more difficult to reduce a latent infection than to prevent infection, since almost all B cells become latently infected. “Thus we think perhaps a role for preventing infection or modifying the initial infection could be important,” said Dr. Cohen.
The most advanced vaccine candidate is a soluble form of EBV glycoprotein gp 350, which is the dominant glycoprotein on the surface of the virus and infected cells. It reduced the risk of mononucleosis by 78%, but it did not prevent EBV infection. There were no safety concerns. Two more vaccines are currently in clinical trials – an mRNA vaccine against a gp 350 sponsored by Moderna, and a gp 350 nanoparticle vaccine by the NIH.
Dr. Cohen acknowledged that safety is the most important factor, since it would be given to healthy individuals, and probably children. There are worries that a vaccine using EBV proteins could worsen MS. In particular, higher titers of antibodies against EBNA have been linked to developing MS and the anti-EBNA antibody has been implicated in molecular mimicry related to MS. However, the current vaccines avoid EBNA. Another worry is that a vaccine could delay onset of disease to an older age, when infection might be more dangerous. However, no delay in onset has been noted with the varicella vaccine or polio vaccines, which prompted similar concerns.
Vaccinating against EBV could also reduce other conditions such as mononucleosis and several cancers.
Does EBV infection even matter?
In his talk, Peter Calabresi, MD, made the case that EBV is not the sole cause of MS, and thus targeting it may prove ineffective. Dr. Calabresi is director of the division of neuroimmunology at Johns Hopkins Medicine, Baltimore.
Why was he asked to provide a rebuttal? “About this time last year, I commented at a meeting that we should be thoughtful as we think about what to do about EBV and MS. I do believe that constructive dialogue is the foundation of science,” he said. He also stated that he is not opposed to vaccines. “I congratulate Dr. Cohen on all of his vaccine successes,” he said.
Still, he is unconvinced that EBV is solely responsible for MS. “I think it’s hard to draw a straight line between EBV and MS as one might with HPV [human papillomavirus] and cervical cancer. For example, we know that EBV accounts for more than 1% of all cancers, and EBV can also cause other autoimmune diseases such as lupus and Sjogren’s, so it’s complicated. And MS of course has genetic susceptibility that’s not limited to the major histocompatibility complex (MHC) genes that are associated with presenting viral peptides,” said Dr. Calabresi.
Evidence relating MS vulnerability to other genetic and environmental factors, including diet, sunlight, smoking, and even pollution, calls into question a direct causal relationship between EBV and MS, he said.
The age prevalence of EBV would complicate efforts to eradicate it. Seroprevalence is 55% by age 5-11 and 75% among university students. “This is important because the duration of the vaccine response–induced protection in young seronegative children is not lengthy. Vaccinated individuals may become susceptible to natural infection at an age where the consequences of infection are more severe, especially leading to infectious mononucleosis, and hopefully not MS. This then raises the issue of the need for boosters, which we’re all well aware of during the COVID pandemic. This may be a problem, especially in young adults due to noncompliance,” said Dr. Calabresi.
He pointed out that not all vaccine attempts went well. In the 1960s, early respiratory syncytial virus (RSV) vaccines caused enhanced respiratory disease and 2 deaths. “We need to be careful when we think about targeting healthy at-risk young people,” said Dr. Calabresi.
Rather than pursue vaccination, Dr. Calabresi favors research into EBV latency in B cells as well as how EBV-infected B cells may cause or exacerbate MS, with the hopes of developing interventions. “It’s tempting to speculate that the success of the anti-CD 20 monoclonal antibody therapies is related to depletion of EBV infected B cells. In fact, I think that may be the case,” he said.
Dr. Cohen has no relevant financial disclosures. Dr. Calabresi has served on a scientific advisory board or data monitoring board for Biogen and Disarm Therapeutics.
SAN DIEGO – Although most adults have been exposed, it is very rare to find MS in an individual with no prior EBV exposure.
That apparent relationship has driven interest in a vaccine against EBV in an effort to reduce MS incidence on a population level.
At a session at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS), two researchers debated the potential benefits and pitfalls of such a program. The issues included the possible benefit in MS and other EBV-related conditions such as mononucleosis and various cancers, and whether EBV infection is a sufficient cause for MS, as well as concerns about vaccinating a healthy at-risk population.
Reducing the risk of MS by targeting EBV
Jeffrey I. Cohen, MD, spoke first, and cited several lines of evidence supporting the importance of EBV in MS. One study showed a 32-fold increased risk of MS following primary infection with EBV, and another showed that higher EBV nuclear antigen (EBNA) antibody titers were associated with a 36-fold higher risk of MS. “So we have two completely independent studies suggesting that EBV is really very important as a cofactor for development of MS,” said Dr. Cohen, chief of the laboratory of infectious diseases and chief of the medical virology section at the National Institutes of Health, Bethesda, Md.
EBV is also latent in B cells, and anti-B cell therapy is an effective therapeutic strategy for MS. However, the mechanism remains unknown.
Targeting EBV could involve attacking infected cells, or a therapeutic vaccine could be employed to treat EVB-infected individuals, similar to the shingles vaccine. “In all of these methods, one would end up with fewer EBV infected B cells and as a result, presumably you’d have reduced antigenic stimulation of EBV-infected B cells to stimulate either antibodies or T cells that could damage the nervous system. By reducing this, one might be able to [treat] multiple sclerosis,” said Dr. Cohen.
He did acknowledge concerns. It isn’t yet understood whether destroying EBV-infected cells would actually improve outcomes. It also may be more difficult to reduce a latent infection than to prevent infection, since almost all B cells become latently infected. “Thus we think perhaps a role for preventing infection or modifying the initial infection could be important,” said Dr. Cohen.
The most advanced vaccine candidate is a soluble form of EBV glycoprotein gp 350, which is the dominant glycoprotein on the surface of the virus and infected cells. It reduced the risk of mononucleosis by 78%, but it did not prevent EBV infection. There were no safety concerns. Two more vaccines are currently in clinical trials – an mRNA vaccine against a gp 350 sponsored by Moderna, and a gp 350 nanoparticle vaccine by the NIH.
Dr. Cohen acknowledged that safety is the most important factor, since it would be given to healthy individuals, and probably children. There are worries that a vaccine using EBV proteins could worsen MS. In particular, higher titers of antibodies against EBNA have been linked to developing MS and the anti-EBNA antibody has been implicated in molecular mimicry related to MS. However, the current vaccines avoid EBNA. Another worry is that a vaccine could delay onset of disease to an older age, when infection might be more dangerous. However, no delay in onset has been noted with the varicella vaccine or polio vaccines, which prompted similar concerns.
Vaccinating against EBV could also reduce other conditions such as mononucleosis and several cancers.
Does EBV infection even matter?
In his talk, Peter Calabresi, MD, made the case that EBV is not the sole cause of MS, and thus targeting it may prove ineffective. Dr. Calabresi is director of the division of neuroimmunology at Johns Hopkins Medicine, Baltimore.
Why was he asked to provide a rebuttal? “About this time last year, I commented at a meeting that we should be thoughtful as we think about what to do about EBV and MS. I do believe that constructive dialogue is the foundation of science,” he said. He also stated that he is not opposed to vaccines. “I congratulate Dr. Cohen on all of his vaccine successes,” he said.
Still, he is unconvinced that EBV is solely responsible for MS. “I think it’s hard to draw a straight line between EBV and MS as one might with HPV [human papillomavirus] and cervical cancer. For example, we know that EBV accounts for more than 1% of all cancers, and EBV can also cause other autoimmune diseases such as lupus and Sjogren’s, so it’s complicated. And MS of course has genetic susceptibility that’s not limited to the major histocompatibility complex (MHC) genes that are associated with presenting viral peptides,” said Dr. Calabresi.
Evidence relating MS vulnerability to other genetic and environmental factors, including diet, sunlight, smoking, and even pollution, calls into question a direct causal relationship between EBV and MS, he said.
The age prevalence of EBV would complicate efforts to eradicate it. Seroprevalence is 55% by age 5-11 and 75% among university students. “This is important because the duration of the vaccine response–induced protection in young seronegative children is not lengthy. Vaccinated individuals may become susceptible to natural infection at an age where the consequences of infection are more severe, especially leading to infectious mononucleosis, and hopefully not MS. This then raises the issue of the need for boosters, which we’re all well aware of during the COVID pandemic. This may be a problem, especially in young adults due to noncompliance,” said Dr. Calabresi.
He pointed out that not all vaccine attempts went well. In the 1960s, early respiratory syncytial virus (RSV) vaccines caused enhanced respiratory disease and 2 deaths. “We need to be careful when we think about targeting healthy at-risk young people,” said Dr. Calabresi.
Rather than pursue vaccination, Dr. Calabresi favors research into EBV latency in B cells as well as how EBV-infected B cells may cause or exacerbate MS, with the hopes of developing interventions. “It’s tempting to speculate that the success of the anti-CD 20 monoclonal antibody therapies is related to depletion of EBV infected B cells. In fact, I think that may be the case,” he said.
Dr. Cohen has no relevant financial disclosures. Dr. Calabresi has served on a scientific advisory board or data monitoring board for Biogen and Disarm Therapeutics.
SAN DIEGO – Although most adults have been exposed, it is very rare to find MS in an individual with no prior EBV exposure.
That apparent relationship has driven interest in a vaccine against EBV in an effort to reduce MS incidence on a population level.
At a session at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS), two researchers debated the potential benefits and pitfalls of such a program. The issues included the possible benefit in MS and other EBV-related conditions such as mononucleosis and various cancers, and whether EBV infection is a sufficient cause for MS, as well as concerns about vaccinating a healthy at-risk population.
Reducing the risk of MS by targeting EBV
Jeffrey I. Cohen, MD, spoke first, and cited several lines of evidence supporting the importance of EBV in MS. One study showed a 32-fold increased risk of MS following primary infection with EBV, and another showed that higher EBV nuclear antigen (EBNA) antibody titers were associated with a 36-fold higher risk of MS. “So we have two completely independent studies suggesting that EBV is really very important as a cofactor for development of MS,” said Dr. Cohen, chief of the laboratory of infectious diseases and chief of the medical virology section at the National Institutes of Health, Bethesda, Md.
EBV is also latent in B cells, and anti-B cell therapy is an effective therapeutic strategy for MS. However, the mechanism remains unknown.
Targeting EBV could involve attacking infected cells, or a therapeutic vaccine could be employed to treat EVB-infected individuals, similar to the shingles vaccine. “In all of these methods, one would end up with fewer EBV infected B cells and as a result, presumably you’d have reduced antigenic stimulation of EBV-infected B cells to stimulate either antibodies or T cells that could damage the nervous system. By reducing this, one might be able to [treat] multiple sclerosis,” said Dr. Cohen.
He did acknowledge concerns. It isn’t yet understood whether destroying EBV-infected cells would actually improve outcomes. It also may be more difficult to reduce a latent infection than to prevent infection, since almost all B cells become latently infected. “Thus we think perhaps a role for preventing infection or modifying the initial infection could be important,” said Dr. Cohen.
The most advanced vaccine candidate is a soluble form of EBV glycoprotein gp 350, which is the dominant glycoprotein on the surface of the virus and infected cells. It reduced the risk of mononucleosis by 78%, but it did not prevent EBV infection. There were no safety concerns. Two more vaccines are currently in clinical trials – an mRNA vaccine against a gp 350 sponsored by Moderna, and a gp 350 nanoparticle vaccine by the NIH.
Dr. Cohen acknowledged that safety is the most important factor, since it would be given to healthy individuals, and probably children. There are worries that a vaccine using EBV proteins could worsen MS. In particular, higher titers of antibodies against EBNA have been linked to developing MS and the anti-EBNA antibody has been implicated in molecular mimicry related to MS. However, the current vaccines avoid EBNA. Another worry is that a vaccine could delay onset of disease to an older age, when infection might be more dangerous. However, no delay in onset has been noted with the varicella vaccine or polio vaccines, which prompted similar concerns.
Vaccinating against EBV could also reduce other conditions such as mononucleosis and several cancers.
Does EBV infection even matter?
In his talk, Peter Calabresi, MD, made the case that EBV is not the sole cause of MS, and thus targeting it may prove ineffective. Dr. Calabresi is director of the division of neuroimmunology at Johns Hopkins Medicine, Baltimore.
Why was he asked to provide a rebuttal? “About this time last year, I commented at a meeting that we should be thoughtful as we think about what to do about EBV and MS. I do believe that constructive dialogue is the foundation of science,” he said. He also stated that he is not opposed to vaccines. “I congratulate Dr. Cohen on all of his vaccine successes,” he said.
Still, he is unconvinced that EBV is solely responsible for MS. “I think it’s hard to draw a straight line between EBV and MS as one might with HPV [human papillomavirus] and cervical cancer. For example, we know that EBV accounts for more than 1% of all cancers, and EBV can also cause other autoimmune diseases such as lupus and Sjogren’s, so it’s complicated. And MS of course has genetic susceptibility that’s not limited to the major histocompatibility complex (MHC) genes that are associated with presenting viral peptides,” said Dr. Calabresi.
Evidence relating MS vulnerability to other genetic and environmental factors, including diet, sunlight, smoking, and even pollution, calls into question a direct causal relationship between EBV and MS, he said.
The age prevalence of EBV would complicate efforts to eradicate it. Seroprevalence is 55% by age 5-11 and 75% among university students. “This is important because the duration of the vaccine response–induced protection in young seronegative children is not lengthy. Vaccinated individuals may become susceptible to natural infection at an age where the consequences of infection are more severe, especially leading to infectious mononucleosis, and hopefully not MS. This then raises the issue of the need for boosters, which we’re all well aware of during the COVID pandemic. This may be a problem, especially in young adults due to noncompliance,” said Dr. Calabresi.
He pointed out that not all vaccine attempts went well. In the 1960s, early respiratory syncytial virus (RSV) vaccines caused enhanced respiratory disease and 2 deaths. “We need to be careful when we think about targeting healthy at-risk young people,” said Dr. Calabresi.
Rather than pursue vaccination, Dr. Calabresi favors research into EBV latency in B cells as well as how EBV-infected B cells may cause or exacerbate MS, with the hopes of developing interventions. “It’s tempting to speculate that the success of the anti-CD 20 monoclonal antibody therapies is related to depletion of EBV infected B cells. In fact, I think that may be the case,” he said.
Dr. Cohen has no relevant financial disclosures. Dr. Calabresi has served on a scientific advisory board or data monitoring board for Biogen and Disarm Therapeutics.
FROM ACTRIMS FORUM 2023