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LJUBLJANA, SLOVENIA – The 4CMenB vaccine didn’t affect carriage of disease-causing genogroups of Neisseria meningitidis in adolescents in the landmark Australian cluster-randomized trial of herd immunity known as the “B Part of It” study, Helen S. Marshall, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.
This was the largest-ever randomized trial of adolescents vaccinated against meningococcal disease, and the message, albeit somewhat disappointing, is clear: “MenB [Meningococcal serogroup B] vaccine programs should be designed to provide direct protection for those at highest risk of disease,” declared Dr. Marshall, professor of vaccinology and deputy director of the Robinson Research Institute at the University of Adelaide.
In other words, Youths in the age groups at highest risk of disease – infants and adolescents – need to routinely receive the vaccine.
The B Part of It study, whose sheer scope and rigor drew the attention of infectious disease clinical trialists the world over, randomized nearly 35,000 students at all high schools in the state of South Australia – whether urban, rural, or remote – to two doses of the 4CMenB vaccine known as Bexsero or to a nonvaccinated control group. This massive trial entailed training more than 250 nurses in the study procedures and involved 3,100 miles of travel to transport oropharyngeal swab samples obtained from students in outlying areas for centralized laboratory analysis using real-time polymerase chain reaction with meningococcal genotyping, culture for N. meningitidis, and whole-genome sequencing. Samples were obtained on day 1 of the study and 12 months later.
The investigators created widespread regional enthusiasm for this project through adept use of social media and other methods. As a result, 99.5% of students randomized to the intervention arm received one dose, while 97% got two doses. A gratifying unintended consequence of the study was that parents who’d never previously vaccinated their children enrolled them in B Part of It, Dr. Marshall noted.
The impetus for B Part of It was that, while the Australian national health insurance program covers a single dose of meningococcal conjugate MenACWY vaccine given at age 12 months and 14-19 years, MenB vaccine isn’t covered because of uncertainties about cost effectiveness and the vaccine’s impact on meningococcal carriage and herd immunity. B Part of It was designed to resolve those uncertainties.
South Australia has the highest rate of invasive meningococcal disease in the country, and more than 80% of cases there are caused by meningococcal serogroup B. Moreover, 75% of group B cases in South Australia involve the nasty hypervirulent New Zealand strain known as CC 41/44.
The primary outcome in B Part of It was the difference in carriage of the major disease-causing serotypes – groups A, B, C, W, X, and Y – between vaccinated and unvaccinated students at the 1-year follow-up mark. The carriage prevalence of all N. meningitidis in the vaccinated students went from 2.8% at baseline to 4.0% at 12 months, and similarly from 2.6% to 4.7% in unvaccinated controls. More importantly, the prevalence of disease-causing genotypes rose from 1.3% at baseline to 2.4% at follow-up in the vaccinated subjects, with a near-identical pattern seen in controls, where the prevalence rose from 1.4% to 2.4%. In an as-treated analysis, the rate of acquisition of carriage of disease-causing genotypes was identical at 2.0% in both study arms.
The 4CMenB vaccine proved reassuringly safe and effective in preventing meningococcal disease in vaccinated teens. With more than 58,000 doses of the vaccine given in the study, no new safety concerns or signals emerged. And the observed number of cases of invasive meningococcal disease in South Australian adolescent vaccine recipients to date has been significantly lower than expected.
Secondary and exploratory outcomes
Independent risk factors associated with N. meningitidis carriage in the study participants at the 1-year mark included smoking cigarettes or hookah, intimate kissing within the last week, and being in grades 11-12, as opposed to grade 10.
The vaccine had no significant impact on the carriage rate of the hypervirulent New Zealand serogroup B strain. Nor was there a vaccine impact on carriage density, as Mark McMillan, MD, reported elsewhere at ESPID 2019. But while the 4CMenB vaccine had minimal impact upon N. meningitidis carriage density, it was associated with a significant 41% increase in the likelihood of cleared carriage of disease-causing strains at 12 months, added Dr. McMillan, Dr. Marshall’s coinvestigator at University of Adelaide.
What’s next
The ongoing B Part of It School Leaver study is assessing carriage prevalence in vaccinated versus unvaccinated high schoolers in their first year after graduating.
In addition, the B Part of It investigators plan to prospectively study the impact of the 4CMen B vaccine on N. gonorrhoeae disease in an effort to confirm the intriguing findings of an earlier large, retrospective New Zealand case-control study. The Kiwis found that recipients of an outer membrane vesicle MenB vaccine had an adjusted 31% reduction in the risk of gonorrhea. This was the first-ever report of any vaccine effectiveness against this major global public health problem, in which antibiotic resistance is a growing concern (Lancet. 2017 Sep 30;390[10102]:1603-10). Dr. Marshall reported receiving research funding from GlaxoSmithKline, which markets Bexsero and was the major financial supporter of the B Part of It study.
But wait a minute...
Following Dr. Marshall’s report on the B Part of It study, outgoing ESPID president Adam Finn, MD, PhD, presented longitudinal data that he believes raise the possibility that protein-antigen vaccines such as Bexsero, which promote naturally acquired mucosal immunity, may impact on transmission population wide without reliably preventing acquisition. This would stand in stark contrast to conjugate meningococcus vaccines, which have a well-established massive impact on carriage and acquisition of N. meningitidis.
It may be that in studying throat carriage rates once in individuals immunized 12 months earlier, as in the B Part of It study, investigators are not asking the right question, proposed Dr. Finn, professor of pediatrics at the University of Bristol (England).
His research team has been obtaining throat swabs at monthly intervals in a population of 917 high schoolers aged 16-17 years. In 416 of the students, they also have collected saliva samples weekly both before and after immunization with 4CMenB vaccine, analyzing the samples for N. meningitidis by polymerase chain reaction. This is a novel method of studying meningococcal carriage they have found to be both reliable and far more acceptable to patients than oropharyngeal swabbing, which adolescents balk at if asked to do with any frequency (PLoS One. 2019 Feb 11;14[2]:e0209905).
Dr. Finn said that their findings, which need confirmation, suggest that N. meningitidis carriage is usually brief and dynamic. They also have found that carriage density varies markedly from month to month.
“We see much higher-density carriage in the adolescent population in the early months of the year in conjunction, we think, with viral infection with influenza and so forth,” he said, adding that this could have clinical implications. “It feels sort of intuitive that someone walking around with 1,000 or 10,000 times as many meningococci in their throat is more likely to be more infectious to people around them with a very small number, although this hasn’t been formally proven.”
He hopes that the Be on the TEAM (Teenagers Against Meningitis) study will help provide answers. The study is randomizing 24,000 U.K. high school students to vaccination with the meningococcal B protein–antigen vaccines Bexsero or Trumenba or to no vaccine in order to learn if there are significant herd immunity effects.
Dr. Finn’s meningococcal carriage research is funded by the Meningitis Research Foundation and the National Institute for Health Research. Dr. Marshall reported receiving research funding from GlaxoSmithKline, the major sponsor of the B Part of It study.
LJUBLJANA, SLOVENIA – The 4CMenB vaccine didn’t affect carriage of disease-causing genogroups of Neisseria meningitidis in adolescents in the landmark Australian cluster-randomized trial of herd immunity known as the “B Part of It” study, Helen S. Marshall, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.
This was the largest-ever randomized trial of adolescents vaccinated against meningococcal disease, and the message, albeit somewhat disappointing, is clear: “MenB [Meningococcal serogroup B] vaccine programs should be designed to provide direct protection for those at highest risk of disease,” declared Dr. Marshall, professor of vaccinology and deputy director of the Robinson Research Institute at the University of Adelaide.
In other words, Youths in the age groups at highest risk of disease – infants and adolescents – need to routinely receive the vaccine.
The B Part of It study, whose sheer scope and rigor drew the attention of infectious disease clinical trialists the world over, randomized nearly 35,000 students at all high schools in the state of South Australia – whether urban, rural, or remote – to two doses of the 4CMenB vaccine known as Bexsero or to a nonvaccinated control group. This massive trial entailed training more than 250 nurses in the study procedures and involved 3,100 miles of travel to transport oropharyngeal swab samples obtained from students in outlying areas for centralized laboratory analysis using real-time polymerase chain reaction with meningococcal genotyping, culture for N. meningitidis, and whole-genome sequencing. Samples were obtained on day 1 of the study and 12 months later.
The investigators created widespread regional enthusiasm for this project through adept use of social media and other methods. As a result, 99.5% of students randomized to the intervention arm received one dose, while 97% got two doses. A gratifying unintended consequence of the study was that parents who’d never previously vaccinated their children enrolled them in B Part of It, Dr. Marshall noted.
The impetus for B Part of It was that, while the Australian national health insurance program covers a single dose of meningococcal conjugate MenACWY vaccine given at age 12 months and 14-19 years, MenB vaccine isn’t covered because of uncertainties about cost effectiveness and the vaccine’s impact on meningococcal carriage and herd immunity. B Part of It was designed to resolve those uncertainties.
South Australia has the highest rate of invasive meningococcal disease in the country, and more than 80% of cases there are caused by meningococcal serogroup B. Moreover, 75% of group B cases in South Australia involve the nasty hypervirulent New Zealand strain known as CC 41/44.
The primary outcome in B Part of It was the difference in carriage of the major disease-causing serotypes – groups A, B, C, W, X, and Y – between vaccinated and unvaccinated students at the 1-year follow-up mark. The carriage prevalence of all N. meningitidis in the vaccinated students went from 2.8% at baseline to 4.0% at 12 months, and similarly from 2.6% to 4.7% in unvaccinated controls. More importantly, the prevalence of disease-causing genotypes rose from 1.3% at baseline to 2.4% at follow-up in the vaccinated subjects, with a near-identical pattern seen in controls, where the prevalence rose from 1.4% to 2.4%. In an as-treated analysis, the rate of acquisition of carriage of disease-causing genotypes was identical at 2.0% in both study arms.
The 4CMenB vaccine proved reassuringly safe and effective in preventing meningococcal disease in vaccinated teens. With more than 58,000 doses of the vaccine given in the study, no new safety concerns or signals emerged. And the observed number of cases of invasive meningococcal disease in South Australian adolescent vaccine recipients to date has been significantly lower than expected.
Secondary and exploratory outcomes
Independent risk factors associated with N. meningitidis carriage in the study participants at the 1-year mark included smoking cigarettes or hookah, intimate kissing within the last week, and being in grades 11-12, as opposed to grade 10.
The vaccine had no significant impact on the carriage rate of the hypervirulent New Zealand serogroup B strain. Nor was there a vaccine impact on carriage density, as Mark McMillan, MD, reported elsewhere at ESPID 2019. But while the 4CMenB vaccine had minimal impact upon N. meningitidis carriage density, it was associated with a significant 41% increase in the likelihood of cleared carriage of disease-causing strains at 12 months, added Dr. McMillan, Dr. Marshall’s coinvestigator at University of Adelaide.
What’s next
The ongoing B Part of It School Leaver study is assessing carriage prevalence in vaccinated versus unvaccinated high schoolers in their first year after graduating.
In addition, the B Part of It investigators plan to prospectively study the impact of the 4CMen B vaccine on N. gonorrhoeae disease in an effort to confirm the intriguing findings of an earlier large, retrospective New Zealand case-control study. The Kiwis found that recipients of an outer membrane vesicle MenB vaccine had an adjusted 31% reduction in the risk of gonorrhea. This was the first-ever report of any vaccine effectiveness against this major global public health problem, in which antibiotic resistance is a growing concern (Lancet. 2017 Sep 30;390[10102]:1603-10). Dr. Marshall reported receiving research funding from GlaxoSmithKline, which markets Bexsero and was the major financial supporter of the B Part of It study.
But wait a minute...
Following Dr. Marshall’s report on the B Part of It study, outgoing ESPID president Adam Finn, MD, PhD, presented longitudinal data that he believes raise the possibility that protein-antigen vaccines such as Bexsero, which promote naturally acquired mucosal immunity, may impact on transmission population wide without reliably preventing acquisition. This would stand in stark contrast to conjugate meningococcus vaccines, which have a well-established massive impact on carriage and acquisition of N. meningitidis.
It may be that in studying throat carriage rates once in individuals immunized 12 months earlier, as in the B Part of It study, investigators are not asking the right question, proposed Dr. Finn, professor of pediatrics at the University of Bristol (England).
His research team has been obtaining throat swabs at monthly intervals in a population of 917 high schoolers aged 16-17 years. In 416 of the students, they also have collected saliva samples weekly both before and after immunization with 4CMenB vaccine, analyzing the samples for N. meningitidis by polymerase chain reaction. This is a novel method of studying meningococcal carriage they have found to be both reliable and far more acceptable to patients than oropharyngeal swabbing, which adolescents balk at if asked to do with any frequency (PLoS One. 2019 Feb 11;14[2]:e0209905).
Dr. Finn said that their findings, which need confirmation, suggest that N. meningitidis carriage is usually brief and dynamic. They also have found that carriage density varies markedly from month to month.
“We see much higher-density carriage in the adolescent population in the early months of the year in conjunction, we think, with viral infection with influenza and so forth,” he said, adding that this could have clinical implications. “It feels sort of intuitive that someone walking around with 1,000 or 10,000 times as many meningococci in their throat is more likely to be more infectious to people around them with a very small number, although this hasn’t been formally proven.”
He hopes that the Be on the TEAM (Teenagers Against Meningitis) study will help provide answers. The study is randomizing 24,000 U.K. high school students to vaccination with the meningococcal B protein–antigen vaccines Bexsero or Trumenba or to no vaccine in order to learn if there are significant herd immunity effects.
Dr. Finn’s meningococcal carriage research is funded by the Meningitis Research Foundation and the National Institute for Health Research. Dr. Marshall reported receiving research funding from GlaxoSmithKline, the major sponsor of the B Part of It study.
LJUBLJANA, SLOVENIA – The 4CMenB vaccine didn’t affect carriage of disease-causing genogroups of Neisseria meningitidis in adolescents in the landmark Australian cluster-randomized trial of herd immunity known as the “B Part of It” study, Helen S. Marshall, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.
This was the largest-ever randomized trial of adolescents vaccinated against meningococcal disease, and the message, albeit somewhat disappointing, is clear: “MenB [Meningococcal serogroup B] vaccine programs should be designed to provide direct protection for those at highest risk of disease,” declared Dr. Marshall, professor of vaccinology and deputy director of the Robinson Research Institute at the University of Adelaide.
In other words, Youths in the age groups at highest risk of disease – infants and adolescents – need to routinely receive the vaccine.
The B Part of It study, whose sheer scope and rigor drew the attention of infectious disease clinical trialists the world over, randomized nearly 35,000 students at all high schools in the state of South Australia – whether urban, rural, or remote – to two doses of the 4CMenB vaccine known as Bexsero or to a nonvaccinated control group. This massive trial entailed training more than 250 nurses in the study procedures and involved 3,100 miles of travel to transport oropharyngeal swab samples obtained from students in outlying areas for centralized laboratory analysis using real-time polymerase chain reaction with meningococcal genotyping, culture for N. meningitidis, and whole-genome sequencing. Samples were obtained on day 1 of the study and 12 months later.
The investigators created widespread regional enthusiasm for this project through adept use of social media and other methods. As a result, 99.5% of students randomized to the intervention arm received one dose, while 97% got two doses. A gratifying unintended consequence of the study was that parents who’d never previously vaccinated their children enrolled them in B Part of It, Dr. Marshall noted.
The impetus for B Part of It was that, while the Australian national health insurance program covers a single dose of meningococcal conjugate MenACWY vaccine given at age 12 months and 14-19 years, MenB vaccine isn’t covered because of uncertainties about cost effectiveness and the vaccine’s impact on meningococcal carriage and herd immunity. B Part of It was designed to resolve those uncertainties.
South Australia has the highest rate of invasive meningococcal disease in the country, and more than 80% of cases there are caused by meningococcal serogroup B. Moreover, 75% of group B cases in South Australia involve the nasty hypervirulent New Zealand strain known as CC 41/44.
The primary outcome in B Part of It was the difference in carriage of the major disease-causing serotypes – groups A, B, C, W, X, and Y – between vaccinated and unvaccinated students at the 1-year follow-up mark. The carriage prevalence of all N. meningitidis in the vaccinated students went from 2.8% at baseline to 4.0% at 12 months, and similarly from 2.6% to 4.7% in unvaccinated controls. More importantly, the prevalence of disease-causing genotypes rose from 1.3% at baseline to 2.4% at follow-up in the vaccinated subjects, with a near-identical pattern seen in controls, where the prevalence rose from 1.4% to 2.4%. In an as-treated analysis, the rate of acquisition of carriage of disease-causing genotypes was identical at 2.0% in both study arms.
The 4CMenB vaccine proved reassuringly safe and effective in preventing meningococcal disease in vaccinated teens. With more than 58,000 doses of the vaccine given in the study, no new safety concerns or signals emerged. And the observed number of cases of invasive meningococcal disease in South Australian adolescent vaccine recipients to date has been significantly lower than expected.
Secondary and exploratory outcomes
Independent risk factors associated with N. meningitidis carriage in the study participants at the 1-year mark included smoking cigarettes or hookah, intimate kissing within the last week, and being in grades 11-12, as opposed to grade 10.
The vaccine had no significant impact on the carriage rate of the hypervirulent New Zealand serogroup B strain. Nor was there a vaccine impact on carriage density, as Mark McMillan, MD, reported elsewhere at ESPID 2019. But while the 4CMenB vaccine had minimal impact upon N. meningitidis carriage density, it was associated with a significant 41% increase in the likelihood of cleared carriage of disease-causing strains at 12 months, added Dr. McMillan, Dr. Marshall’s coinvestigator at University of Adelaide.
What’s next
The ongoing B Part of It School Leaver study is assessing carriage prevalence in vaccinated versus unvaccinated high schoolers in their first year after graduating.
In addition, the B Part of It investigators plan to prospectively study the impact of the 4CMen B vaccine on N. gonorrhoeae disease in an effort to confirm the intriguing findings of an earlier large, retrospective New Zealand case-control study. The Kiwis found that recipients of an outer membrane vesicle MenB vaccine had an adjusted 31% reduction in the risk of gonorrhea. This was the first-ever report of any vaccine effectiveness against this major global public health problem, in which antibiotic resistance is a growing concern (Lancet. 2017 Sep 30;390[10102]:1603-10). Dr. Marshall reported receiving research funding from GlaxoSmithKline, which markets Bexsero and was the major financial supporter of the B Part of It study.
But wait a minute...
Following Dr. Marshall’s report on the B Part of It study, outgoing ESPID president Adam Finn, MD, PhD, presented longitudinal data that he believes raise the possibility that protein-antigen vaccines such as Bexsero, which promote naturally acquired mucosal immunity, may impact on transmission population wide without reliably preventing acquisition. This would stand in stark contrast to conjugate meningococcus vaccines, which have a well-established massive impact on carriage and acquisition of N. meningitidis.
It may be that in studying throat carriage rates once in individuals immunized 12 months earlier, as in the B Part of It study, investigators are not asking the right question, proposed Dr. Finn, professor of pediatrics at the University of Bristol (England).
His research team has been obtaining throat swabs at monthly intervals in a population of 917 high schoolers aged 16-17 years. In 416 of the students, they also have collected saliva samples weekly both before and after immunization with 4CMenB vaccine, analyzing the samples for N. meningitidis by polymerase chain reaction. This is a novel method of studying meningococcal carriage they have found to be both reliable and far more acceptable to patients than oropharyngeal swabbing, which adolescents balk at if asked to do with any frequency (PLoS One. 2019 Feb 11;14[2]:e0209905).
Dr. Finn said that their findings, which need confirmation, suggest that N. meningitidis carriage is usually brief and dynamic. They also have found that carriage density varies markedly from month to month.
“We see much higher-density carriage in the adolescent population in the early months of the year in conjunction, we think, with viral infection with influenza and so forth,” he said, adding that this could have clinical implications. “It feels sort of intuitive that someone walking around with 1,000 or 10,000 times as many meningococci in their throat is more likely to be more infectious to people around them with a very small number, although this hasn’t been formally proven.”
He hopes that the Be on the TEAM (Teenagers Against Meningitis) study will help provide answers. The study is randomizing 24,000 U.K. high school students to vaccination with the meningococcal B protein–antigen vaccines Bexsero or Trumenba or to no vaccine in order to learn if there are significant herd immunity effects.
Dr. Finn’s meningococcal carriage research is funded by the Meningitis Research Foundation and the National Institute for Health Research. Dr. Marshall reported receiving research funding from GlaxoSmithKline, the major sponsor of the B Part of It study.
REPORTING FROM ESPID 2019