In the Journals

One dose of pneumococcal vaccine plus booster effective in UK study

A single dose plus a booster of the 13-valent pneumococcal conjugate vaccine was equal or superior to the current two-dose plus booster schedule for most targeted serotypes in a recent study.

The findings suggest that fewer doses of Prevnar 13 (PCV13; Wyeth Pharmaceuticals) can offer less costly coverage, at least in areas with stable pneumococcal immunity, the study researchers wrote in The Lancet Infectious Diseases.

“Our data suggest that booster responses following a 1+1 schedule are unlikely to compromise long-term control of invasive pneumococcal disease when administered in a setting where PCV coverage, particularly for the booster dose, is high at the local, regional and national level, PCV has been used for some years and pneumococcal disease and carriage of vaccine serotypes has already been controlled in all age groups,” researcher David Goldblatt, PhD, a professor of vaccinology and immunology at University College London, and colleagues wrote.

For their study, the researchers enrolled infants in the United Kingdom between September 2015 and June 2016.

They randomly assigned 106 infants to receive the current two-dose plus booster schedule of PCV13 (2+1, group 1). Those infants were vaccinated at 2, 4 and 12 months. 

Another 107 infants were randomly assigned to receive the 1+1 schedule (group 2). They were vaccinated at 3 and 12 months. The median infant ages were 60 days in group 1 and 59 days in group 2.

A month after booster vaccination, 91 serum samples were available from group 1 and 86 were available from group 2. They were assessed for serotype-specific geometric mean concentrations (GMC) of immunoglobulin G.

According to the researchers, the GMCs for groups 1 and 2, respectively, were equivalent for serotypes 3 (0.61 and 0.62 µg/mL), 5 (1.74 and 2.11 µg/mL), 7F (3.98 and 3.36 µg/mL), 9V (2.34 and 2.50 µg/mL) and 19A (8.38 and 8.83 µg/mL).

But group 2 — those infants receiving the 1+1 schedule — had significantly higher GMCs for serotypes 1 (8.92 vs 3.07 µg/mL), 4 (3.43 vs 2.55 µg/mL), 14 (16.9 vs 10.49 µg/mL) and 19F (14.76 vs 11.12 µg/mL).

Group 1 had higher GMCs for serotypes 6A (8.62 vs 6.36 µg/mL), 6B (6.19 vs 2.39 µg/mL), 18C (1.98 vs 1.63 µg/mL) and 23F (2.87 vs 1.72 µg/mL).

Among a subset of 40 infants — 19 from group 1 and 21 from group 2 — functional serotype-specific antibody responses were similar, the researchers said.  Although the results suggest the 1+1 schedule is effective in a high-income country like the U.K., Goldblatt and colleagues warned that they probably would not hold true in developing countries.

“These conditions are currently likely to only be met in high-income countries, and thus extrapolating this study’s finding to the current situation in low- and middle-income countries should be made with caution,” they wrote.

They added, however, that work is already under way in assessing a shorter PCV schedule in developing countries.

“A number of randomized, controlled studies comparing a 1+1 PCV schedule with existing immunization schedules in India, South Africa, Vietnam and Gambia are currently under way,” the researchers wrote. “These, together with invasive pneumococcal disease surveillance and carriage studies, will provide a comprehensive evidence base for future decisions about global PCV immunization strategies.”

In related commentary, Katherine L. O’Brien, MD, a professor in the departments of international health and epidemiology at the Johns Hopkins Bloomberg School of Public Health, wrote that shorter PCV schedules could fill a critical global need.

She noted that PCV prices can reach as high as $169 per dose in the United States. Although Gavi, the Vaccine Alliance, provides PCV doses cheaply to very poor countries, it does not do so for middle-income countries, O’Brien wrote.

She added that even lower income countries may no longer have full Gavi support when their economies improve.

“Strategies to reduce PCV program costs, without compromising disease protection, need to be pursued,” O’Brien explained. Although she agreed with Goldblatt and colleagues that the prospect for shorter PCV schedules in lower income countries requires more research, she also touted the strategy’s potential benefits.

“In spite of all the constraints on which countries might meet epidemiological conditions that would allow a switch to a 1+1 schedule, it is estimated that savings of roughly $1.5 billion could be accrued over a 10-year time period in Gavi-eligible countries alone,” O’Brien wrote, citing previous research. “That would be a compelling ‘less is more’ proposition.” – by Joe Green

Disclosures: Goldblatt has served on ad-hoc advisory boards for GlaxoSmithKline, Merck and Sanofi Pasteur and is a National Institute of Health Research senior investigator. The University College of London Great Ormond Street Institute of Child Health Lab, with which Goldblatt is affiliated, has received contract research funding from GlaxoSmithKline, Merck and Sanofi. Please see the study for all other authors’ relevant financial disclosures. O’Brien reports grants from Pfizer, GlaxoSmithKline, Gavi and the Bill and Melinda Gates Foundation, as well as other contributions from Merck, outside her submitted commentary. She also reports serving with the WHO Strategic Advisory Group of Experts on Immunization.

A single dose plus a booster of the 13-valent pneumococcal conjugate vaccine was equal or superior to the current two-dose plus booster schedule for most targeted serotypes in a recent study.

The findings suggest that fewer doses of Prevnar 13 (PCV13; Wyeth Pharmaceuticals) can offer less costly coverage, at least in areas with stable pneumococcal immunity, the study researchers wrote in The Lancet Infectious Diseases.

“Our data suggest that booster responses following a 1+1 schedule are unlikely to compromise long-term control of invasive pneumococcal disease when administered in a setting where PCV coverage, particularly for the booster dose, is high at the local, regional and national level, PCV has been used for some years and pneumococcal disease and carriage of vaccine serotypes has already been controlled in all age groups,” researcher David Goldblatt, PhD, a professor of vaccinology and immunology at University College London, and colleagues wrote.

For their study, the researchers enrolled infants in the United Kingdom between September 2015 and June 2016.

They randomly assigned 106 infants to receive the current two-dose plus booster schedule of PCV13 (2+1, group 1). Those infants were vaccinated at 2, 4 and 12 months. 

Another 107 infants were randomly assigned to receive the 1+1 schedule (group 2). They were vaccinated at 3 and 12 months. The median infant ages were 60 days in group 1 and 59 days in group 2.

A month after booster vaccination, 91 serum samples were available from group 1 and 86 were available from group 2. They were assessed for serotype-specific geometric mean concentrations (GMC) of immunoglobulin G.

According to the researchers, the GMCs for groups 1 and 2, respectively, were equivalent for serotypes 3 (0.61 and 0.62 µg/mL), 5 (1.74 and 2.11 µg/mL), 7F (3.98 and 3.36 µg/mL), 9V (2.34 and 2.50 µg/mL) and 19A (8.38 and 8.83 µg/mL).

But group 2 — those infants receiving the 1+1 schedule — had significantly higher GMCs for serotypes 1 (8.92 vs 3.07 µg/mL), 4 (3.43 vs 2.55 µg/mL), 14 (16.9 vs 10.49 µg/mL) and 19F (14.76 vs 11.12 µg/mL).

Group 1 had higher GMCs for serotypes 6A (8.62 vs 6.36 µg/mL), 6B (6.19 vs 2.39 µg/mL), 18C (1.98 vs 1.63 µg/mL) and 23F (2.87 vs 1.72 µg/mL).

Among a subset of 40 infants — 19 from group 1 and 21 from group 2 — functional serotype-specific antibody responses were similar, the researchers said.  Although the results suggest the 1+1 schedule is effective in a high-income country like the U.K., Goldblatt and colleagues warned that they probably would not hold true in developing countries.

“These conditions are currently likely to only be met in high-income countries, and thus extrapolating this study’s finding to the current situation in low- and middle-income countries should be made with caution,” they wrote.

They added, however, that work is already under way in assessing a shorter PCV schedule in developing countries.

“A number of randomized, controlled studies comparing a 1+1 PCV schedule with existing immunization schedules in India, South Africa, Vietnam and Gambia are currently under way,” the researchers wrote. “These, together with invasive pneumococcal disease surveillance and carriage studies, will provide a comprehensive evidence base for future decisions about global PCV immunization strategies.”

In related commentary, Katherine L. O’Brien, MD, a professor in the departments of international health and epidemiology at the Johns Hopkins Bloomberg School of Public Health, wrote that shorter PCV schedules could fill a critical global need.

She noted that PCV prices can reach as high as $169 per dose in the United States. Although Gavi, the Vaccine Alliance, provides PCV doses cheaply to very poor countries, it does not do so for middle-income countries, O’Brien wrote.

She added that even lower income countries may no longer have full Gavi support when their economies improve.

“Strategies to reduce PCV program costs, without compromising disease protection, need to be pursued,” O’Brien explained. Although she agreed with Goldblatt and colleagues that the prospect for shorter PCV schedules in lower income countries requires more research, she also touted the strategy’s potential benefits.

“In spite of all the constraints on which countries might meet epidemiological conditions that would allow a switch to a 1+1 schedule, it is estimated that savings of roughly $1.5 billion could be accrued over a 10-year time period in Gavi-eligible countries alone,” O’Brien wrote, citing previous research. “That would be a compelling ‘less is more’ proposition.” – by Joe Green

Disclosures: Goldblatt has served on ad-hoc advisory boards for GlaxoSmithKline, Merck and Sanofi Pasteur and is a National Institute of Health Research senior investigator. The University College of London Great Ormond Street Institute of Child Health Lab, with which Goldblatt is affiliated, has received contract research funding from GlaxoSmithKline, Merck and Sanofi. Please see the study for all other authors’ relevant financial disclosures. O’Brien reports grants from Pfizer, GlaxoSmithKline, Gavi and the Bill and Melinda Gates Foundation, as well as other contributions from Merck, outside her submitted commentary. She also reports serving with the WHO Strategic Advisory Group of Experts on Immunization.