ACIP: Fifty Years of Vaccine Recommendations Continue with an Eye Towards Safety and Efficacy
This year marks the 50th anniversary of the Advisory Committee on Immunization Practices (ACIP).
The Committee, founded by the Surgeon General in 1964, originally consisted of 10 members and included influenza vaccine as one of its first agenda items. When the committee convened last week to continue their ongoing efforts to develop safe and effective vaccine recommendations, there were over 50 members present and influenza was once again on the agenda.
The changes in immunization recommendations in the past fifty years have been nothing short of astounding. Not only do we continue to see new vaccines, but we have exceptional standards in place to evaluate the increased safety and efficacy of these new recommendations. The Committee’s commitment to the public is exemplified by the great lengths they take to examine all the evidence prior to making their recommendations.
After an extensive review of the data compiled by a special Influenza Working Group, a unanimous decision was made by the ACIP to recommend the Live Attenuated Influenza Vaccine (LAIV), commonly referred to as the nasal mist vaccine, as the preferred influenza vaccine to be administered to healthy 2-8 year olds when available. Through their further review of the scientific research presented at the February meeting, the Committee found that LAIV was a more effective vaccine for this age group. The studies also confirmed that there were no identifiable safety concerns that would prevent the Committee from recommending LAIV over the Inactivated Influenza Vaccine (IIV), commonly referred to as the flu shot.
While the recommendation can be applauded for providing better flu protection among a vulnerable age group, there were some concerns that the recommendation comes too late in the year. Most pediatric providers have already submitted their vaccine supply orders for the upcoming flu season and without anticipating this new recommendation they may not have ordered enough LAIV to accommodate their patients. It is also unknown whether the vaccine manufacturer has planned to produce enough vaccine to meet the public’s demand. To help address these concerns, the Committee emphasized that while LAIV is preferred, if it is not immediately available, the injectable vaccine should be used and vaccination should not be delayed.
It should be noted that some people should not receive the live attenuated influenza vaccine. (For details of the ACIP’s specific recommendations and a list of those with LAIV contraindications, click here.) Also, regardless of whether children receive the LAIV or IIV, the recommendation remains that children, age 6 months through 8 years of age, should receive 2 doses of flu vaccine in the first year that they are vaccinated for influenza.
In addition to voting on influenza vaccine recommendations, the Committee also heard various presentations related to influenza vaccine safety.
For instance, Dr. Maria Cano of the CDC gave a complete overview of the end-of-season 2013-14 influenza vaccine safety monitoring. She reviewed specific VAERS reports and demonstrated that there were no signals of any concerning outcomes. She explained that surveillance for the upcoming 2014-15 influenza season will be expanded to include enhanced safety monitoring for quadrivalent vaccines, cell culture based and recombinant based IIV, reports in persons with a history of egg allergy after IIV and LAIV and reports in persons with a history of asthma and wheezing after LAIV.
While LAIV appears to be more effective than IIV in children, the Committee continued to investigate whether there is concern regarding an increased risk in fever following LAIV versus IIV vaccination. Dr. Melissa Stockwell, of Columbia University, gave a presentation that focused on children ages 24-59 months during the 2013-14 influenza season. She found no significant difference in the fever rates at or over 100.4 degrees Fahrenheit on vaccination day or in the first 2 days post vaccination with LAIV versus IIV and no evidence of any significant difference in fever rates 3-10 days post vaccination either. Of course, the Committee will continue to investigate the data and address any concerns in regards to the safety of influenza vaccine recommendations.
After spending two days at a public ACIP meeting, anyone can see that the Committee is committed to making recommendations that are in the best interest of the public. Following each meeting, the presentation slides are posted on the CDC website and a live webcast ensures that meetings are accessible to the public, even if they are unable to travel to Atlanta.
Of course, in addition to influenza discussions, there were plenty of other agenda topics that were covered at this meeting to include the following:
Yellow Fever Vaccine
In May 2014, the World Health Organization (WHO) adopted new recommendations in regards to Yellow Fever vaccine. Beginning in June they no longer recommend a Yellow Fever booster every 10 years. Before the ACIP modifies their own recommendations to forego the need for a booster dose, they took the time at the June meeting to review the data in order to ensure that a single dose of vaccine would be sufficient to confer sustained life-long protective immunity against Yellow Fever disease. The ACIP working group determined that while the data does suggest that a single dose of vaccine can provide long-lasting protection for most travelers, there were concerns that some populations may remain at a greater risk of disease and may benefit from a continued booster recommendation.
These populations could possibly include laboratory workers, long-term travelers, young children who appear to have a low (17%) seroconversion rate as noted in the available data, and those with underlying medical conditions that might compromise their immune system such as HIV infected persons, those who have received bone marrow transplantation, and pregnant women who are at greater risk for Yellow Fever infection. Before the ACIP is willing to make a recommendation that mirrors the WHO’s changes, they want to make sure they are considering the full ramifications. The decision was made that additional studies may need to be conducted and the working group would need to report back to the Committee with consolidated recommendations before a vote could be held at a future meeting.
Human Papillomavirus (HPV) Vaccine
The good news is that there is a new 9-valent HPV vaccine making its way through the final stages of clinical trials and the data indicates that it has a 97% efficacy in the prevention of 5 additional HPV types for a total protection against 9 different HPV strains. The Committee is currently investigating whether the new vaccine will offer the same high level of safety and tolerability as the current quadrivalent HPV vaccine so that when the new 9-valent HPV vaccine is licensed, which is expected to happen by December, the Committee will be prepared to vote on a new HPV recommendation at the February 2015 meeting.
In preparation, they are reviewing the current clinical trial data which has indicated that the safety profile is comparable to the current quadrivalent vaccine, with most reactions being limited to mild or moderate injection site irritation. However, in addition to investigating the safety of the new vaccine, there has been some simultaneous discussion as to whether an HPV vaccine could offer a similarly high level of protection when administered in two doses as opposed to three.
Remaining questions include whether there are differences in duration of protection for a 2 dose versus 3 dose schedule, whether longer follow-up is needed from these studies, and whether there should be a change in interval between shots if the number of doses is reduced. Since some countries have adopted a 2 dose schedule and have also modified the intervals, the Committee is considering whether available data from these other countries may be used to investigate the effectiveness of adopting a 2 dose schedule here. Unfortunately the 9-valent vaccine will likely be licensed by the FDA in December 2014 and voted on at the ACIP meeting in February 2015, while the potential data from a 2 dose clinical trial will not be available until October 2015.
So we are left wondering whether the Committee will make a 3 dose recommendation for the new 9-valent HPV vaccine in February and then later consider changing it to a 2 dose schedule, or whether they will have evidence to switch to a 2 dose recommended schedule that coincides with the recommendation of the new 9-valent HPV vaccine? The answer will likely hinge on what data is available to them and when.
There was a great deal of time spent reviewing studies of febrile seizures following administration of multiple vaccines. Dr. Alison Kawai, of Harvard Medical School, gave a presentation that analyzed the risk of febrile seizures during the 2010-11 influenza season which concluded that vaccination with both a trivalent influenza vaccine and PCV13 in the same day during the 2010-11 season did not result in elevated risk of febrile seizure when compared to separate day vaccine administration. Dr. Jonathan Duffy of the CDC also presented a Vaccine Safety Data analysis study to assess whether vaccines other than PCV13 given with trivalent influenza may affect the risk of febrile seizure. In conclusion, the analysis found that the concomitant administration of trivalent influenza, plus PCV and DTaP containing vaccines had higher risk of febrile seizures than when the vaccines were given independently. These increased risks with concomitant vaccination were observed in all influenza seasons studied and not just during the 2010-11 season.
While it’s important to remember that although frightening for parents and caregivers, febrile seizures do not have lasting effects and are fairly common in young children. They can happen with any condition that causes a fever. However, these reports demonstrate the methodical way in which the Committees concerns about vaccine safety and adverse events are thoroughly investigated with numerous reports on the same subject to ensure that both the Committee and the public remain well-informed.
Pneumococcal Conjugate Vaccine (PCV)
In February 2010, the ACIP recommended that healthcare providers transition from use of PCV7 to the use of PCV13 for routine vaccination of children. Then, in late 2011, a supplement was issued to the FDA license to expand the use of PCV13 in adults. Now that PCV13 vaccine is licensed for adults age 50 years and above, the ACIP is considering a universal recommendation for its use in the adult population. Presentations made to the Committee have revealed that there is a definite public health burden as a result of pneumococcal pneumonia in adults, and found that the PCV13 vaccine would reduce the incidence of disease and hospitalization while also saving on medical expenditures resulting from infection.
Policy options under consideration by the working group include adding a dose of PCV13 to the currently recommended pneumococcal vaccine regime for those 65 years and older, and replacing a dose of one pneumonia vaccine (PPSV23) with a dose of PCV13. It was interesting to hear the working group’s explanation that although universal PCV13 use is warranted in the short-term, the expected benefits of the herd effects over time will likely mean that a universal recommendation will not be needed long-term. Since the policy options under consideration are rather complex and generated a fair amount of discussion at the meeting, the Committee was not able to bring a recommendation to a vote. Knowing that it would be critical to implement any new recommendations before the 2014-15 respiratory season begins, the working group agreed to draft acceptable policy language that would attempt to address all concerns and will consider holding a vote by phone before the October 2014 meeting.