Ask the Experts: ACIP addresses range of vaccine topics at recent meeting
Committee discusses issues surrounding influenza, meningococcal, pneumococcal, and human papillomavirus vaccines, among others.
The Advisory Committee on Immunization Practice (ACIP) met in Atlanta, GA, on October 23–24, 2013. Complete minutes of the meeting will be published on the ACIP website.
The meeting was opened by Thomas R. Frieden, MD, MPH, CDC Director. He welcomed new members and expressed his appreciation to ACIP for their role in protecting public health.
The recent publication of the 2013–14 ACIP influenza recommendations included new vaccine strains, licensure of six new influenza vaccines, and clarification of egg allergies. Since the publication of the report, Flulaval Quadrivalent (ID Biomedical) was licensed and Flulaval Trivalent was approved for a new age indication (patients >3 years).
As of October 12, influenza activity was low, which is normal for this early in the influenza season. About 90% of the strains reported so far are type A. Influenza-like illness (ILI) activity remains low.
Vaccination coverage rates for the 2012–13 season were reviewed. A total of 134.9 million doses were distributed last season, with coverage rates of 57% in children, 41.5% in adults older than 18 years, and 66% in individuals 65 years or older. Rates were higher in all age groups. Health care worker coverage rates from a recent Morbidity and Mortality Weekly Report publication also were reviewed.
National Influenza Vaccination Week will be December 8–14.
A summary of the Fluzone High-Dose (Sanofi Pasteur) vaccine efficacy trial results was presented. The prelicensure trials demonstrated that the vaccine induced a statistically significantly higher antibody response against all three strains compared with regular-dose Fluzone vaccine. Fluzone High-Dose is indicated for adults 65 years or older, while regular-dose Fluzone is recommended for patients 6 months or older.
A study comparing the clinical efficacy of Fluzone High-Dose with Fluzone trivalent vaccine was presented. The study enrolled approximately 32,000 participants 65 years or older in 128 study sites over two influenza seasons. The study was designed to compare the efficacy with respect to laboratory-confirmed influenza caused by any influenza strain with the occurrence of protocol-defined ILI. Relative efficacy was 24.2% higher for Fluzone High-Dose (1.43% vs. 1.89% ILI). Slight improvement also was seen for pneumonia, hospitalizations, and cardiorespiratory episodes. Additional analysis and studies are under way.
Three conjugated meningococcal vaccines have been approved in the United States. MenACYW-135-CRM (Menveo—Novartis) recently received an indication for age a early as 2 months (2 months to 55 years). The studies submitted for FDA approval were presented. The vaccine demonstrated effective blood titers and did not interfere with other vaccines given in the infant series. The GRADE analysis was similar to the other meningococcal vaccines. The working group decided that Menveo should be added as an option for vaccinating high-risk infants.
Yellow fever vaccine
New recommendations were made by the World Health Organization (WHO) for use of booster doses of yellow fever vaccine. The Strategic Advisory Group of Experts (SAGE) of WHO recommends a single dose of yellow fever vaccine without boosters, as it appears to be sufficient to protect for a lifetime. Currently, ACIP recommends a booster every 10 years for the United States. YF-Vax (Sanofi Pasteur) is licensed in the United States; it is indicated for individuals traveling to endemic areas of the world. The Yellow Fever Working Group will evaluate data and develop recommendations to determine whether ACIP should follow the WHO recommendation. If changes are to be made, an ACIP vote is anticipated during 2014.
Many countries have implemented pneumococcal conjugate vaccine (PVC) in a three-dose schedule (compared with the four-dose schedule in the United States). CDC has been evaluating the incidence of invasive pneumococcal disease (IPD) in children since 2010 (when 13-valent PCV [PCV13] was licensed) and is observing a decline. Also, as a result of herd effect, IPD appears to be declining in adults. The vaccine effectiveness in one study against all IPD in children was 65%. However, if vaccine effectiveness is measured against the PCV13 serotypes in the vaccine, it climbs to 89%.
Because WHO recognizes a three-dose schedule as acceptable, the working group is discussing a reduction in the number of doses in the pneumococcal childhood series. We also are seeing a large decline in disease burden in the United States caused by serotypes in the vaccine. Looking at studies from other countries, the vaccine effectiveness ranged from 70% to 100% against vaccine-type IPD. The vaccines used in these studies included PCV7, -9, and -13. The four-dose series studies reported a vaccine effectiveness of 81% to 100%. No studies comparing three- and four-dose schedules have emerged. Differing types of studies (e.g., randomized controlled versus observational) and differing diseases (e.g., IPD, pneumonia, acute otitis media) are under way.
In conclusion, the three-dose PCV studies demonstrate effectiveness against IPD, pneumonia, and otitis media. The immunogenicity studies demonstrate that after the primary series, three doses are more effective than two, but this difference does not continue after the second year of life. Also, little difference is noted after the booster dose for the two-plus-one versus three-plus-one series. The same pattern was seen with nasopharyngeal carriage. However the differences may not be meaningful because PCV7 serotypes rarely cause disease and the PVC13 serotype disease is disappearing. The herd effects are similar, so changes at the population level are not expected.
A great deal of discussion occurred regarding this recommendation. The working group will reevaluate.
Herpes zoster vaccine
The herpes zoster vaccine was approved for a single dose in patients 60 years or older in 2006. FDA approved the vaccine for ages 50 through 59 years in 2011; however, ACIP did not change its recommendations as a result of supply issues and lack of data on long-term protection. The committee agreed to continue monitoring the situation and revisit its recommendation in the future. The supply issue has been resolved. However, uptake of vaccine continues to be low, with only 20% of adults older than 60 years receiving the vaccine.
A representative from Merck reviewed long-term persistence of the zoster vaccine up to 12 years postvaccination but did not present any conclusions on the data.
The burden of herpes zoster disease increases with age while vaccine efficacy decreases. The Shingles Prevention Study (SPS) demonstrated a vaccine efficacy of 51% for participants 60 years or older. The Zostavaz Efficacy and Safety Trial (ZEST) trial of adults aged 50 to 59 years showed a vaccine efficacy of 70%. Persistence was studied during the SPS and was only carried out for 7 years.The short-term vaccine efficacy decreased during this time period. Long-term effectiveness was difficult to estimate in adults 60 years or older due to a lack of a concurrent control group. Cost-effectiveness analysis also showed that it was more cost effective to vaccinate at 60 or 70 compared with 50 years of age.
The working group did not propose changes to the existing recommendations for routine vaccination of people 60 years or older. Evidence demonstrating long-term protection with the vaccine is not sufficient, and individuals receiving the vaccine at younger than 60 years may not be protected when the incidence of herpes zoster and its complications are highest.
Update on global immunizations
Jon S. Abramson, MD, Chair of WHO's SAGE, provided an overview of the advisory group's progress during the previous few years. SAGE consists of 15 experts from around the world serving a 3-year term and collaborates with WHO organizations regarding vaccines.
About 17,000 fewer children younger than 5 years of age die every day in 2012 compared with 1990. However, 18,000 children younger than 5 still die each day, and many of these deaths are vaccine preventable. Most of the issues occur in Africa and Asia. A total of 90 million lives have been saved since 1990, but more than 216 million children have died. If millennium development goals are achieved, an incremental 3.5 million lives could be saved between now and 2015.
The interaction among SAGE, the Decade of Vaccines Collaboration, and the Global Vaccine Action Plan was reviewed with an emphasis on achieving a polio-free world, meeting global and regional elimination targets, meeting coverage targets, and introducing new vaccines.
Human papillomavirus vaccine
An update on human papillomavirus (HPV) vaccine coverage in the United States was presented, as well as a review of the development program for 9-valent HPV and a briefing on updating the ACIP statement.
As of 2012, 53% of girls had received one dose of HPV and 33% all three doses. The vaccination rate for boys is 21% for one dose and 7% for all three doses. These are much lower than the rates for other adolescent vaccines, and unlike other vaccines, trends in coverage rates seem to be flattening out.
The top five reasons for low HPV vaccine coverage rates were (1) not needed, (2) not recommended by provider, (3) safety concerns/adverse effects, (4) lack of knowledge about the vaccine, and (5) not sexually active. Provider recommendations and eliminating missed opportunities are considered critical to improving coverage rates.
Merck has an investigational 9-valent HPV vaccine that would increase coverage rates to 90% for cervical cancer and up to 85% for precancers. The 9-valent vaccine contains serotypes 31, 33, 45, 52, and 58 in addition to 6, 11, 16, and 18 in the current vaccine. The vaccine is virus-like particle based, alum adjuvanted, and will be administered in a three-dose series. The target age is the same as that for the quadrivalent vaccine.
The ACIP recommendation statement for HPV vaccine has not been updated since 2007. The statement is being revised to reflect the policy notes, clear up inconsistencies, and provide additional data that have been generated. ACIP will review the updated statement and probably vote at the next meeting.
Child and adolescent immunization schedules
Changes to the child and adolescent immunization schedules were minor. Some footnote changes were made, and Menveo was included in the table. The schedule was approved by ACIP and will be published in January or February 2014.
Adult immunization schedule
ACIP recommendations for vaccination are based on age, previous vaccinations, health status, lifestyle, occupations, and travel. Potential reasons for vaccination rates being very low currently include limited awareness of the public, lack of provider recommendations, and lack of assessment of vaccination status at health care visits.
NVAC approved new Standards for Adult Immunization Practices in September 2013. These are meant to help increase adult immunization rates. The full recommendations are expected to be published in March 2014 in Public Health Reports.
Changes to the adult immunization table include moving the PPSV23 (23-valent pneumococcal polysaccharide vaccine) bar below the PCV13 bar. Also, a bar was added for Hib in high-risk patients. As with the childhood schedule, many footnotes were edited for clarity. The adult immunization schedule was approved by ACIP and will be published in January or February 2014.
Andrew Kroger, MD, MPH, Medical Officer, CDC National Center for Immunization and Respiratory Diseases, reviewed the changes that the working group had made to the General Recommendations on Immunization.
The presentation focused on vaccine administration and vaccine records. The topics for review were changes to infection control and sterile technique, revising the language on Occupational Safety and Health Administration regulations, information on vaccination route (e.g., intradermal versus subcutaneous), provider records, and Immunization Information Systems.
The Clinical Decision Support for Immunization (CDSI) project was described. CDSI resources help provide clarity and consistency to ACIP recommendations in computer systems.
The next meeting will be February 26–27, 2014, in Atlanta, GA.