HUMAN VACCINES & IMMUNOTHERAPEUTICS 2016, VOL. 12, NO. 7, 1906–1907 http://dx.doi.org/10.1080/21645515.2016.1147638
LETTER
Pneumococcal conjugate vaccine in adults: Let’s see what happens Peter R. Paradiso Paradiso Biologics Consulting, LLC, Radnor, PA, USA
ABSTRACT
ARTICLE HISTORY
The recent recommendation for the use of the 13-valent pneumococcal conjugate vaccine (PCV13) in adults 65 y of age and older, provides a new tool for preventing disease in this at-risk population. The conjugate vaccine induces a T-cell dependent response, which distinguishes it from the polysaccharide vaccine and could provide the longer-term protection necessary to have a significant impact in this population.
Received 7 January 2016 Accepted 22 January 2016
Dear Editor, Musher and Rodriquez-Barradas1 have once again outlined the issues that have revolved around the licensure of a pneumococcal conjugate vaccine for adults and its potential to provide a direct benefit against pneumococcal disease in that population. The issues were recently well reviewed by Schuchat et al.2 and separately Hochman3 et al. expressing opposing views. The elephant in the room regarding the polysaccharide vaccine is that in the US, it has been recommended for adults 65 y of age and older for 3 decades. During that time, 60-70% of adults have been vaccinated with the polysaccharide vaccine and many vaccinated on more than one occasion. The dilemma facing recommending bodies is that, over that time, there has been no measurable impact on invasive pneumococcal disease, let alone pneumonia, caused by the serotypes in the vaccine. The apparent lack of benefit is not because we are unable to measure it – the CDC’s ABC surveillance system does an excellent job in that regard. When PCV7 was introduced into the infant population in 2000, the indirect effect in adults was easily identified. In contrast, in the years after 2000, the incidence of disease caused by the serotypes not in the PCV7 vaccine increased in older adults, driven in part by serotype 19A, which is included in the polysaccharide vaccine.4,5 Perhaps the most relevant recent experience with the polysaccharide vaccine occurred in the UK where the vaccine was introduced in a stepwise fashion to adults over 65 y of age starting in 2003. Andrews et al.6 studied the impact of the vaccine in this highly immunized population in the years following the inception of the program. What they found was effectiveness against invasive pneumococcal disease in the period within 2 y after vaccination but little consistent or significant impact beyond that. In addition they showed clearly that cases caused by the nonPCV7 serotypes in the polysaccharide vaccine increased in the years after the adult immunization program began. This outcome is the earmark of a polysaccharide vaccine where CONTACT Peter R. Paradiso © 2016 Taylor & Francis
[email protected]
immunity wanes quickly along with antibody titer with no pathway to renew that immunity upon exposure to the pathogen. If the polysaccharide provides only a few years of immunity in the lifetime of an adult over 65 y of age, it is mathematically not surprising that this impact has not been measurable. The recently published CAPiTA trial referred to by Musher and Rodriquez-Barradas1 had a very important outcome beyond the efficacy against IPD and pneumonia and that was the duration of that protection.7 It appeared that the protection was sustained over the 4-year period of the trial – a time during which antibody titers wane significantly. This result is consistent with our understanding of conjugate vaccines as T-dependent antigens and gives some hope for more durable protection in adults at increased risk for pneumococcal disease. With the implementation of the13-valent conjugate vaccine recommendation in the US, we will have the ability to measure the impact of this intervention directly. While the indirect effect of the childhood vaccination program will be a confounder, there will be ample populations of unvaccinated adults to make effectiveness calculations possible. As with most routinely recommended vaccines, we will see the results soon.
Disclosure of potential conflicts of interest The author is a consultant for and holds stock in Pfizer, Inc.
References [1] Musher DM, Rodriguez-Barradas MB. Why the recent ACIP recommendations regarding conjugate pneumococcal vaccine in adults may be irrelevant. Hum Vaccin Immunother 2015; 12(2): 331-5; PMID:26606172; http://dx.doi.org/10-1080/21645515.2015.1098794 [2] Schuchat A. Pneumococcal prevention gets older and wiser. JAMA Intern Med 2015; 175:1897-8; PMID:26502379; http://dx.doi.org/ 10.1001/jamainternmed.2015.6133 [3] Hochman M, Cohen PA. Reconsidering guidelines on the use of pneumococcal vaccines in adults 65 years or older. JAMA Intern Med
129 Woods Lane, Radnor, PA USA.
HUMAN VACCINES AND IMMUNOTHERAPEUTICS
2015; 175:1895-6; PMID:26502317; http://dx.doi.org/10.1001/ jamainternmed.2015.5689 [4] Moore MR, Whitney CG. Use of pneumococcal disease epidemiology to set policy and prevent disease during 20 years of the emerging infections program. Emerging Inf Dis 2015; 21:1551-56; PMID:26291238; http://dx.doi.org/10.3201/eid2109.150395 [5] Pilishvili T, Lexau C, Farley MM et al. Sustained reductions in invasive pneumococcal disease in the Era of conjugate vaccines. JID 2010; 201:32-41; PMID:19947881; http://dx.doi.org/10.1086/648593
1907
[6] Andrews A, Waight PA, George RC et al. Impact and effectiveness of 23-valent pneumococcal polysaccharide vaccine against invasive pneumococcal disease in the elderly in England and Wales. Vaccine 2012; 30:6802-8; PMID:23000122; http://dx.doi.org/10.1016/ j.vaccine.2012.09.019 [7] Bonten MJ, Huijts SM, Bolkenbaas M, et al. Polysaccharide conjugate vaccine against pneumococcal pneumonia in adults. N Engl J Med 2015; 372:1114-25; PMID:25785969; http://dx.doi.org/10.1056/ NEJMoa1408544
LETTER
Pneumococcal conjugate vaccine in adults: Let’s see what happens Peter R. Paradiso Paradiso Biologics Consulting, LLC, Radnor, PA, USA
ABSTRACT
ARTICLE HISTORY
The recent recommendation for the use of the 13-valent pneumococcal conjugate vaccine (PCV13) in adults 65 y of age and older, provides a new tool for preventing disease in this at-risk population. The conjugate vaccine induces a T-cell dependent response, which distinguishes it from the polysaccharide vaccine and could provide the longer-term protection necessary to have a significant impact in this population.
Received 7 January 2016 Accepted 22 January 2016
Dear Editor, Musher and Rodriquez-Barradas1 have once again outlined the issues that have revolved around the licensure of a pneumococcal conjugate vaccine for adults and its potential to provide a direct benefit against pneumococcal disease in that population. The issues were recently well reviewed by Schuchat et al.2 and separately Hochman3 et al. expressing opposing views. The elephant in the room regarding the polysaccharide vaccine is that in the US, it has been recommended for adults 65 y of age and older for 3 decades. During that time, 60-70% of adults have been vaccinated with the polysaccharide vaccine and many vaccinated on more than one occasion. The dilemma facing recommending bodies is that, over that time, there has been no measurable impact on invasive pneumococcal disease, let alone pneumonia, caused by the serotypes in the vaccine. The apparent lack of benefit is not because we are unable to measure it – the CDC’s ABC surveillance system does an excellent job in that regard. When PCV7 was introduced into the infant population in 2000, the indirect effect in adults was easily identified. In contrast, in the years after 2000, the incidence of disease caused by the serotypes not in the PCV7 vaccine increased in older adults, driven in part by serotype 19A, which is included in the polysaccharide vaccine.4,5 Perhaps the most relevant recent experience with the polysaccharide vaccine occurred in the UK where the vaccine was introduced in a stepwise fashion to adults over 65 y of age starting in 2003. Andrews et al.6 studied the impact of the vaccine in this highly immunized population in the years following the inception of the program. What they found was effectiveness against invasive pneumococcal disease in the period within 2 y after vaccination but little consistent or significant impact beyond that. In addition they showed clearly that cases caused by the nonPCV7 serotypes in the polysaccharide vaccine increased in the years after the adult immunization program began. This outcome is the earmark of a polysaccharide vaccine where CONTACT Peter R. Paradiso © 2016 Taylor & Francis
[email protected]
immunity wanes quickly along with antibody titer with no pathway to renew that immunity upon exposure to the pathogen. If the polysaccharide provides only a few years of immunity in the lifetime of an adult over 65 y of age, it is mathematically not surprising that this impact has not been measurable. The recently published CAPiTA trial referred to by Musher and Rodriquez-Barradas1 had a very important outcome beyond the efficacy against IPD and pneumonia and that was the duration of that protection.7 It appeared that the protection was sustained over the 4-year period of the trial – a time during which antibody titers wane significantly. This result is consistent with our understanding of conjugate vaccines as T-dependent antigens and gives some hope for more durable protection in adults at increased risk for pneumococcal disease. With the implementation of the13-valent conjugate vaccine recommendation in the US, we will have the ability to measure the impact of this intervention directly. While the indirect effect of the childhood vaccination program will be a confounder, there will be ample populations of unvaccinated adults to make effectiveness calculations possible. As with most routinely recommended vaccines, we will see the results soon.
Disclosure of potential conflicts of interest The author is a consultant for and holds stock in Pfizer, Inc.
References [1] Musher DM, Rodriguez-Barradas MB. Why the recent ACIP recommendations regarding conjugate pneumococcal vaccine in adults may be irrelevant. Hum Vaccin Immunother 2015; 12(2): 331-5; PMID:26606172; http://dx.doi.org/10-1080/21645515.2015.1098794 [2] Schuchat A. Pneumococcal prevention gets older and wiser. JAMA Intern Med 2015; 175:1897-8; PMID:26502379; http://dx.doi.org/ 10.1001/jamainternmed.2015.6133 [3] Hochman M, Cohen PA. Reconsidering guidelines on the use of pneumococcal vaccines in adults 65 years or older. JAMA Intern Med
129 Woods Lane, Radnor, PA USA.
HUMAN VACCINES AND IMMUNOTHERAPEUTICS
2015; 175:1895-6; PMID:26502317; http://dx.doi.org/10.1001/ jamainternmed.2015.5689 [4] Moore MR, Whitney CG. Use of pneumococcal disease epidemiology to set policy and prevent disease during 20 years of the emerging infections program. Emerging Inf Dis 2015; 21:1551-56; PMID:26291238; http://dx.doi.org/10.3201/eid2109.150395 [5] Pilishvili T, Lexau C, Farley MM et al. Sustained reductions in invasive pneumococcal disease in the Era of conjugate vaccines. JID 2010; 201:32-41; PMID:19947881; http://dx.doi.org/10.1086/648593
1907
[6] Andrews A, Waight PA, George RC et al. Impact and effectiveness of 23-valent pneumococcal polysaccharide vaccine against invasive pneumococcal disease in the elderly in England and Wales. Vaccine 2012; 30:6802-8; PMID:23000122; http://dx.doi.org/10.1016/ j.vaccine.2012.09.019 [7] Bonten MJ, Huijts SM, Bolkenbaas M, et al. Polysaccharide conjugate vaccine against pneumococcal pneumonia in adults. N Engl J Med 2015; 372:1114-25; PMID:25785969; http://dx.doi.org/10.1056/ NEJMoa1408544
