The CDC’s Advisory Committee on Immunization Practice (ACIP) met in Atlanta, GA, on June 25–26, 2014. Complete minutes of the meeting will be published on the ACIP website.
At the February ACIP meeting, evidence was presented showing that live attenuated influenza vaccine (LAIV) has a slight advantage over inactivated influenza vaccine (IIV) in preventing laboratory-confirmed influenza (i.e., 46 fewer cases per 1,000 vaccinations) and otitis media (i.e., 6 fewer cases per 1,000) for children aged 2 to 8 years. Limited data for other measures—such as influenza-like illness, medically attended acute respiratory infection, and hospitalizations—support this advantage.
Based on this evidence, the ACIP voted to preferentially recommend the LAIV for use in children 2 to 8 years of age when product is available.
The 2014–15 influenza recommendations will state that all individuals older than 6 months of age should receive influenza vaccination. Vaccination should not be delayed to obtain a specific vaccine preparation when another is available. LAIV should be given preferentially for healthy children age 2 to 8 years who have no contraindications; however, if LAIV is not immediately available, clinicians should administer the IIV. There should be no delay in administering the influenza vaccine to procure the LAIV formulation.
ACIP also noted that the vaccine strains for the 2014–15 season will be the same as in 2013–14. Infants and children normally need two doses of influenza vaccine the first time they are immunized and one dose each season after that. For infants and children who received their first influenza immunization last season but only received one dose, one dose of this season’s vaccine will provide adequate immunogenicity.
Influenza vaccine safety monitoring over the last season was also presented. Using data from the Vaccine Adverse Event Reporting System (VEARS) and the Vaccine Safety Datalink (VSD), no safety signals were identified for trivalent or quadravalent inactivated influenza vaccines (IIV3 or IIV4), Flucelvax—Novartis, the intradermal vaccine, or Flublok—Protein Sciences. Most reactions were local inflammation reactions.
Another study examined fever rates in children ages 24 to 59 months after live and inactivated vaccines. A daily text message was sent to each parent following vaccination with either LAIV or IIV. Fever was defined as any temperature greater than 100.4⁰ F and considered moderate if it was greater than 102.2⁰ F. A total of 535 patients were enrolled, and coadministered vaccines were recorded. For days 0 to 2, fever rates were 5.8% for the IIV and 3.8% for LAIV groups. The data showed that there were no difference in fever rates, fever was rare, and no hospitalizations or febrile seizures occurred with either vaccine.
Additional safety data gathered over the last several influenza seasons indicated that simultaneous vaccination of IIV3 with pneumococcal conjugate vaccine (PCV) or diphtheria, tetanus, and pertussis (DTaP) was associated with a slight increase in febrile seizures (i.e., 38 cases per 100,000 children vaccinated). The increase was noted to be transient (days 0 to 1) and without lasting effects; therefore, ACIP felt that no changes to the current recommendations were warranted.
Finally, presenters told ACIP that the influenza vaccine supply for the 2014–15 season is expected to be 153 million to 158 million doses.
As mentioned at the February ACIP meeting, a three-dose, 13-valent pneumococcal conjugate vaccine (PCV13) schedule is used in many other countries, while the United States currently has a 4-dose schedule. The ACIP working group was tasked to re-evaluate the current U.S. schedule.
CDC has been monitoring invasive pneumococcal disease (IPD) and evaluating serotypes that have caused disease. The serotypes in the PCV7 have virtually disappeared, and the serotypes in PCV13 vaccine are rapidly disappearing. A GRADE analysis for reducing the number of doses of PCV13 in the pediatric scheduledemonstrated that there was limited evidence which compared 3 doses vs 4 doses, but again, serotype changes are expected to affect the outcomes. The working group noted that it was still not ready to make a recommendation for change but will continue its evaluation.
The Community-Acquired Pneumonia Immunization Trial in Adults (CAPiTA) results were also presented. This Phase IV trial of PCV13 in adults was performed in the Netherlands. While PCV13 was licensed by FDA for adults older than 50 years, the ACIP has not recommended this use. CAPiTA was a randomized, controlled trial of Pfizer’s PCV13 (Prevanar 13) compared with placebo in 84,496 patients older than 65 years. The primary study tested the efficacy of PCV13 in preventing vaccine-serotype pneumococcal community-acquired pneumonia (CAP). CAP was diagnosed based on two or more clinical findings consistent with pneumonia, positive chest X-ray, and positive culture of Streptococcus pneumoniae from blood, pleural or other sterile site, and/or a positive urine test. The trial reported a 46% reduction in CAP, with 49 cases in the vaccine group compared with 90 cases in the placebo group.
The ACIP working group was tasked to consider if PCV13 should be routinely administered to all adults 65 years or older. Members estimated that the number needed to treat (NNT) to prevent a single case of PCV13-type invasive pneumococcal disease was 20,400; 1,620 for inpatient CAP; and 1,110 for outpatient CAP. The GRADE analysis supported the use of PCV13 in adults; however, herd immunity may limit the need for PCV13 in the future. Thus, ACIP concluded that a short-term recommendation may be warranted. Proper sequencing may make the schedule more complicated and difficult. Also, there are payment issues with CMS; only one dose of pneumococcal vaccine is covered for beneficiaries older than 65. Since a timely decision is needed for the 2014–15 respiratory season, the committee may meet over the summer to discuss this issue further.
ACIP discussed the recent outbreaks of meningococcal disease occurring in the United States, but noted that the incidence is decreasing. While cases of serogroup C, Y, and B have been reported, outbreaks of type B are more prevalent due to the high vaccination coverage of adolescents with the meningococcal conjugate vaccine (MenACWY). Three outbreaks at universities across the country have occurred with meningococcal type B.
During these outbreaks, CDC provided a meningococcal type B vaccine available in other countries through an Investigational New Drug (IND) application. A two-dose series of this vaccine, which is not licensed by FDA, was recommended. Administration began in December 2013 for all students and selected faculty and staff considered at high risk at the affected universities. Guidelines developed by CDC were presented to ACIP. These will be published soon. ACIP noted that two manufacturers are currently fast tracking a meningococcal B vaccine for application to FDA.
Yellow fever is a mosquito-borne disease that causes 200,000 to 300,000 deaths annually in equatorial Africa and South America. While several vaccines against this disease are used around the world, YF-Vax(Sanofi Pasteur) is approved for use in the United States. The vaccine is recommended for persons 9 months of age or older travelling or living in areas at risk. It is given in a single subcutaneous dose at intervals of 10 years. Many contraindications and precautions exist and careful screening must be performed. Reviews of the literature show that 90% of vaccine recipients have high antibodies at 10 to 20 years. High titers have been detected as long as 60 years postvaccination, and very few vaccine failures have been reported.
In April 2013, the Strategic Advisory Group of Experts for the World Health Organization recommended elimination of the yellow fever vaccine booster dose. A GRADE analysis was applied by the ACIP working group; however, very few data are available. The working group recommended booster doses no longer be administered for most travelers or laboratory workers. After discussion by several experts against the recommendation based on limited data, ACIP postponed the vote until the next meeting.
Clinical data on the new 9-valent human papillomavirus (HPV) vaccine by Merck were presented, continuing the presentation introduced at February’s meeting. The 9-valent HPV vaccine has proven to be very effective (97%) in reduction of disease caused by the new HPV serotypes and noninferior to the serotypes in the original vaccine. In addition, the safety profile appears to be similar to that of the original vaccine, with most adverse drug events being local reactions.
Two other studies have been completed with three vaccines marketed by Sanofi Pasteur, including a concomitant administration trial with Menacta and Adacel and another with Repevax (diphtheria, tetanus, acellular pertussis, and polio vaccines). There was no decrease in titers due to administration with these vaccines. In addition, giving the 9-valent HPV to those who have received the 4-valent HPV resulted in no safety issues and was highly immunogenic.
Based on these studies, the 9-valent HPV vaccine will be licensed for girls and women ages 9 to 26 years and for boys 9 to 15 years of age. Another analysis was performed for men ages 16 to 26 years who have sex with men, and a GRADE analysis will be presented at the next ACIP meeting. Studies have been performed evaluating a two-dose schedule, and the working group is evaluating to see if decreasing to two doses from the current three doses should be considered. Several countries have lowered the recommended doses.
Extending the interval between the doses may be an important issue, and several ongoing trials are evaluating this. The ACIP working group plans to evaluate the 9-valent HPV vaccine and compare a two- versus three-dose schedule.
The last ACIP recommendation for typhoid vaccine was in 1994. Two vaccines are currently available in the United States. ACIP recommendations will be updated to reflect new information on epidemiology, vaccine safety, and vaccine availability.
The hepatitis working group is starting to update the ACIP recommendations for both hepatitis A and hepatitis B, which date back to 2006. They will be re-evaluating the current high-risk groups and consider vaccination of exposed patients older than 40 years. Several interim recommendations have been made and will be incorporated into the new recommendations.
One of the most extensive sections of the General Recommendations, Altered Immunocompetence, has been revised. This follows the release of new Infectious Disease Society of America (IDSA) guidelines in December 2013.
There are a few discrepancies between the two guidelines and ACIP is attempting to address these. Each specific vaccine working group will address the issues and report back to the General Recommendations Working Group. A new classification of degree of immunosuppression (high vs. low) has been published in the IDSA guidelines. ACIP will attempt to incorporate this into the General Recommendations. In addition, there were a few changes in the Vaccination Programs section, and this entire document will be discussed and voted upon at the October ACIP meeting.
There are currently two pediatric schedules (child/adolescent and catch-up schedules). They are fairly complicated. A working group will try to simplify the schedule using “job aids,” a type of algorithm in a table format for individual vaccines. A few of these algorithms have been field tested and were well received. In the future, CDC will develop job aids for more vaccines.