Updates to vaccine recommendations focus of ACIP's October meeting
Complete information will be available on CDC’s website in January and February 2015
CDC’s Advisory Committee on Immunization Practice (ACIP) meet in Atlanta, GA, October 29–30, 2014, to discuss vaccine recommendations. Following is a summary of the committee's decisions.
ACIP reported that influenza activity was low but the season was just starting. Last season, hospitalization rates were highest in those 65 years and older; however, 57% of cases were in the 18- to 64-year-old group (highest rate in this group since the pandemic). Type A(H1N1) was predominant in the early part of the season, whereas type B increased toward the end of the year. This year, while it’s too early to predict accurately, type A(H3N2) and B viruses are predominant.
The committee presented an update on the effectiveness of the live attenuated influenza vaccine (LAIV; FluMist—MedImmune) and the injectable vaccines over the last three influenza seasons among individuals 2 to 18 years of age. The type of circulating virus changed every year. For LAIV, effectiveness against medically attended influenza was 60%, 46%, and 0% during the 2011–12, 2012–13, and 2013–14 seasons, respectively. Note that the numbers enrolled in this study were small for the 2- to 8-year-old cohort. Inactivated influence vaccine (IIV) effectiveness was 61%, 47%, and 60%, respectively. Therefore, the relative effectiveness favored the LAIV in 2011–12 season and the IIV for the 2013–14 season, with no difference during the 2012–13 season. Since the A(H1N1) virus was predominant in the 2013–14 season, perhaps LAIV was not effective against this virus.
MedImmune was asked to respond to the findings and found similar results but observed some differences by vaccine lot that may be explained by potency loss of the A(H1N1) strain resulting from temperature control issues. Another MedImmune study found that early shipments of the vaccine showed loss of effectiveness and higher effectiveness later in the season. A Department of Defense study also found low to negative vaccine effectiveness for LAIV in this last season. This is incongruent with ACIP’s decision in June 2014 to preferentially recommend LAIV for children aged 2 to 8 years of age on the basis of earlier studies. The committee hopes that surveillance during this current season will help determine the cause of these findings.
A presentation was made by the medical director of bioCSL, manufacturer of the Afluria influenza vaccine, on its use with the Pharma-jet Stratus needle-free system. The Lancet study used in the FDA approval was also described. In evaluations of immunogenicity, safety, and patient preference, the geometric mean titers and seroconversion rates for jet injection compared with needle were nearly identical. There were more patient complaints with the jet injector, but all issues were resolved in a few days. Safety issues also were comparable.
ACIP reported that vaccine distribution was slower in the beginning this year because of manufacturer issues, but no further delays have occurred. A projected 151 to 156 million doses will be distributed this year, compared with 134.5 million doses last year. Supply issues with pertussis–containing vaccines are resolved; however, GlaxoSmithKline’s diphtheria–tetanus–acellular pertussis vaccine, DTaP–IPV (Kinrix), has had some shipping delays. In addition, no hepatitis A and hepatitis B (recombinant) vaccines (Twinrix—GlaxoSmithKline) are available.
ACIP’s 2014–15 influenza recommendation was published August 15, 2014, in the Morbidity and Mortality Weekly Report.
A new working group has been established for the H5N1 vaccine. The A(H5N1) virus is a highly pathogenic avian influenza virus that first emerged in Hong Kong in 1997. Human cases usually involve contact with dead birds. A total of 687 cases in 16 countries were reported between 2003 and 2014, with 393 deaths (59%). No human-to-human transmission has occurred. As the virus evolves, vaccines must also change to keep current. Currently, the vaccine is indicated for laboratory workers and other health care workers who may be exposed to this virus. Four vaccines are in the current U.S. stockpile, with one licensed by FDA and one lot of 100,000 doses being manufactured.
Unlike other influenza vaccines available in the United States, H5N1 is an adjuvanted vaccine given in two doses 21 days apart. It is anticipated that this vaccine may be used in laboratory workers, experimental animal study workers, and public health responders (both human and animal). CDC has estimated that approximately 2,845 individuals in this group may be at risk and need this vaccine. Between 2007 and 2013, there were 44 reported incidents or exposures; however, no infections have occurred in this group.
Current recommendations for tetanus–diphtheria–acellular pertussis (Tdap) and tetanus–diphtheria (Td) are as follows:
- Single dose of Tdap for all persons aged 11 years and older
- Pregnant women with every pregnancy at 27 to 36 weeks’ gestation
- Td every 10 years if person has received Tdap
Currently, only 15% of adults have received Tdap. During the June 2013 meeting, the ACIP decided that it would not recommend routine revaccination with Tdap, except for select populations. This decision was based on data showing modest efficacy (75%) during the first year and rapidly waning titers. At that time, the recommendation for vaccination of pregnant women during every pregnancy was made. The working group also decided that it would look into revaccination of select populations, one of which is health care providers.
The working group concluded that while pertussis transmission in hospitals does occur, the risk to health professionals is unclear because of lack of studies. At this time, there is no evidence that additional doses would be beneficial in preventing disease in the health care setting, and the working group did not recommend a change in the current recommendations. Studies are continuing and will be evaluated as they are completed.
The working group was tasked with updating the hepatitis A recommendation. The universal recommendation for all children aged 12 months to 23 months was made in 2006. Older children catch-up recommendations were also made at this time. Other recommendations included high-risk groups and prophylaxis for exposed individuals.
The rates of hepatitis A–reported cases dropped from 59,606 cases in 1972 to 1,298 cases in 2011. Slight increases have been seen since 2011. Only the 0 to 9 years of age group has reached the Healthy People 2020 rates of fewer than 0.3 cases per 100,000 population. In addition, the age of patients hospitalized for hepatitis A increased from 37.6 in 2002 to 45.5 in 2011. Imported fruits and vegetables are a common source of infection.
Vaccination rates of hepatitis A is low in all age groups for which the vaccine is recommended. The working group will continue to discuss strategies to increase these vaccination rates.
FDA approved a new meningococcal B vaccine on October 29, 2014 (Trumenba–Pfizer). This vaccine was approved for ages 10 years to 25 years and is administered on a three-dose schedule at 0, 2, and 6 months. It is a bivalent vaccine against two protein subfamilies. This was studied with serum bactericidal assay using human complement (hSBA), which was demonstrated to correlate with protection at a greater than fourfold increase in titers and a minimum response titer of greater than 1:16. This vaccine met these requirements against four common meningococcal strains seen in the United States. Adverse effects were primarily local. The vaccine was also shown to be safe when administered with HPV4 and Tdap–IPV vaccines.
Novartis has an investigational vaccine, 4CMenB (Bexsero), under FDA review that contains four antigenic components. Given in a two-dose schedule, the vaccine is expected to cover 91% to 92% of meningococcal B strains. Clinical trials showed persistent antibody titers at 18 to 23 months postvaccination and an excellent safety profile, with local reactions the most common adverse effect. The vaccine is already approved in 30 other countries and was used during the recent outbreak in the United States.
The working group discussed the epidemiology of meningococcal disease. Serogroup B causes about 40% of all diseases in college-age groups (about 50 cases per year). There have been 43 cases of meningococcal type B disease reported in the literature in high-risk groups. The incidence of all meningococcal disease is declining, including serotype B, in part because of widespread use of the MenACWY vaccine in the United States. The working group is discussing the potential use for these vaccines, including in high-risk groups and adolescents. However, additional data are needed (e.g., on duration of protection, breadth of coverage, safety and immunogenicity for other age groups).
Recommendations for typhoid vaccination, last published in 1994, will be updated to provide more current information. Some proposed updates include the following:
- Current travel recommendations, as the countries where vaccine is indicated has changed and drug resistance is higher
- Clarification of the definition of chronic carrier
- Clarification of the indication for laboratory workers
- New data on vaccine availability, typhoid epidemiology, and vaccine efficacy and safety
New data were presented on the 9-valent human papillomavirus vaccine (HPV9) that was submitted to FDA in December 2013. This vaccine covers 90% of the high-risk HPV types that cause cancer in humans. The 9-valent vaccine is manufactured the same way as the 4-valent vaccine (Gardasil), with the same adjuvant. Immunobridging studies (efficacy based on similar titers) was performed in adolescents and men and compared with studies in young women. The adverse effect profile is similar to the 4-valent vaccine (HPV4). Data demonstrated a decrease in gynecological procedures (biopsies and therapeutic procedures) in HPV9-vaccinated patients compared with HPV4-vaccinated patients.
Evaluating the cost effectiveness of changing to a 9-valent vaccine was modeled. Currently, the 4-valent program is cost effective, and changing to a 9-valent program is more cost-effective and potentially cost-saving. Most of the cost effectiveness is seen in girls, primarily due to a reduction in cases of cervical cancer. Impact depends on vaccine uptake and duration of protection, both of which are unpredictable. It is expected that one additional case of cervical cancer will be prevented for every 1,000 individuals vaccinated with HPV9 instead of HPV4.
A GRADE (Grading of Recommendations Assessment, Development, & Evaluation) analysis—a systematic approach to making a decision based on the quality of evidence and strength of recommendation—will be conducted and presented at the February ACIP meeting.
The working group is also evaluating a two-dose versus a 3-dose schedule for the HPV vaccine. Current vaccine coverage for girls is approximately 38% for the three-dose series. Results of immunogenicity studies comparing the two versus three-doses were similar; however, effectiveness was slightly lower. In addition, the duration of protection as evaluated by antibody levels appeared to be shorter in the two-dose schedule compared with the three-dose schedule. Several countries around the world are using the two-dose schedules. There is also an ongoing trial using the 9-valent vaccine in a two-dose schedule.
The 9-valent vaccine, expected to be licensed by December 2014, is a three-dose schedule. It will probably be licensed for females aged 9 to 26 years and males aged 9 to 15 years of age. The working group will make policy suggestions after the vaccine is approved but does not expect to recommend revaccination of those already given HPV4 with HPV9.
ACIP reviewed and/or voted to accept the following:
- Febrile seizures and vaccinations (recognition of increase in febrile seizures (1/2,200 doses) with the combination of IIV and the 13-valent pneumococcal conjugate vaccine, PCV13 (Prevnar 13—Pfizer): ACIP recommended no change in recommendation to administer these vaccines together.
- Vaccination during anesthesia/surgery/hospitalization: there was a question of decreased immune response, but the studies were inconsistent and did not provide convincing evidence to be an issue with vaccination. The general recommendations were reworded to state that efforts should be made to vaccinate during hospitalization or before discharge. Current or recent anesthesia/surgery/hospitalization is not a contraindication to vaccination.
- Safe injection practices: multidose vials should not be stored in patient treatment areas.
- Nonstandard vaccination practices: in some vaccination practices, some patients (e.g., those with hemophilia) are given vaccines subcutaneously instead of intramuscularly. Without studies, ACIP recommends repeating the doses intramuscularly except for the quadrivalent meningococcal conjugate vaccine, MenACWY-CRM (Menveo—Novartis), and hepatitis A vaccines. There was no evidence to make a decision about DTaP, Haemophilus influenzae type B vaccine (Hib), and PCV13.
- PCV13 and the pneumococcal polysaccharide vaccine, PPSV23 (Pneumovax 23—Merck), should not be given simultaneously.
Childhood immunization schedule
There were no major changes in recommendations, which will be published on CDC’s website in January 2015. ACIP approved the schedule by vote.
Adult immunization schedule
Changes to the adult schedule include the following:
- PCV13 recommendation changes on schedule for adults with immunocompromised conditions and those aged 65 years and older
- Footnote changes for influenza and pneumococcal vaccines (these pneumococcal changes were very complicated and difficult to incorporate into the schedule)
This schedule was approved by ACIP and will be published on CDC’s website in January or February 2015.
The Vaccine Adverse Event Reporting System (VAERS) form will be updated. Changes will include updating the data fields, making the form electronic only, and modernizing its design. The proposed new form has been reviewed by CDC, FDA, a panel of users, and other advisory groups. More reviews, including public comments, will continue.
Complete minutes of the meeting are available on CDC’s Vaccinations & Immunizations Web page.