Ask the Experts: ACIP addresses variety of vaccine topics at latest meeting
Committee discusses issues surrounding pneumococcal, Japanese encephalitis, and many other vaccines.
The Advisory Committee on Immunization Practice (ACIP) met in Atlanta, GA, on February 20–21, 2013. Complete minutes of the meeting will be published on the ACIP website.
The 13-valent pneumococcal conjugate vaccine (PCV13; Prevnar—Wyeth) was recently approved by FDA for use in children aged 6 to 18 years. Although there is no indication for this vaccine in healthy children in this age group, indications do exist for vaccination of children with certain chronic diseases.
Use of PCV7 (7-valent pneumococcal conjugate vaccine) in children resulted in a decrease in pneumococcal disease in adults, and monitoring of its effects with additional serotypes (PCV13) is ongoing. Data have been collected that demonstrate the decrease in invasive pneumococcal disease in children during the last 3 years. In 2011, a decrease in disease among adults appeared to occur as a result of the new serotypes in the vaccine.
Currently, PCV13 has a permissive recommendation for use in PCV13-naive children with asplenia, cochlear implants, cerebrospinal fluid leaks, HIV, chronic renal failure, and other immunodeficient conditions. Because the vaccine is now FDA approved, ACIP voted to make this a routine recommendation. No changes were made to the recommendations for use of PPSV23 (i.e., two doses separated by 5 years).
Haemophilus influenza vaccine
The last ACIP recommendation regarding Haemophilus influenza (Hib) vaccine was published in 1993, and no changes to the routine use of Hib have been made since that time. Available vaccines on the U.S. market are as follows:
- Polysaccharide-protein conjugate (PRP) vaccines
- PRP-OMP (PedvaxHIB—Merck); 1990: 2, 4 months; booster at 12–15 months
- PRP-T (ActHIB—Sanofi Pasteur): 1993: 2, 4, 6 months; booster at 12–15 months
- PRP-T (Hiberix—GlaxoSmithKline); 2009: booster dose only
- Combination vaccines
- PRP-OMB/Hep B (Comvax—Merck); 1996: 2, 4, 6 months; booster at 12–15 months
- PRP-T/DTaP/IPV (Pentacel—Sanofi Pasteur); 2008: 2, 4, 6 months; booster at 15–18 months
- PRP-T/MenCY (MenHibRix—GlaxoSmithKline); June 2012: 2, 4, 6 months; booster at 12–15 months booster; only if meningococcal vaccine is indicated
Guidance for special populations, high-risk groups, and chemoprophylaxis for Hib will be clarified in the new statement.
HibMenCY was recommended by ACIP for use only in meningococcal high-risk groups.
Japanese encephalitis vaccine
Japanese encephalitis (JE) is a serious disease with no treatment, and many infected patients either die or have permanent neurological deficiencies. The only available JE vaccine is Ixiario (Intercell Biomedical), and it is only approved for patients 17 years or older. JE-Vax (Biken) was indicated for use in children older than 2 years, but it was discontinued. Currently, only three pediatric clinical trials are being conducted for Ixiario. FDA approval is under way for use in children 2 months through 16 years and expected to be decided in May 2013. Current recommendations for the use of JE vaccine were reviewed. When approved for children, it will be discussed by ACIP.
The CDC Immunization Safety Office (ISO) provides extensive monitoring for vaccine safety. This is accomplished through surveillance, investigation, research, and communication/education. The main projects at ISO are the Vaccine Adverse Event Reporting System (VAERS), Vaccine Safety Datalink (VSD), and Clinical Immunization Safety Assessment.
An epidemic of pertussis continues in the United States, with more than 41,000 cases reported in 2012. The current recommendation for Tdap (tetanus–diphtheria–acellular pertussis) vaccine is one dose for everyone older than 10 years followed by Td (tetanus–diphtheria) vaccine every 10 years. The other new indication is for Tdap to be administered during every pregnancy. Safety monitoring of Tdap in pregnancy is under way. No safety signals have been reported through VAERS. VSD, which is a network of providers monitored by CDC, has three clinical studies of Tdap in pregnancy under way, but it is too early for results.
The incidence of pertussis continues to increase; the switch from whole-cell pertussis to acellular vaccine could help to explain the increase in disease. Another finding is that although pertussis titers are high for 1 to 2 years after acellular pertussis vaccination, they decrease rapidly after this time period.
Tdap booster dose was presented, with clinical trials showing safety and immunogenicity. ACIP will discuss the GRADE (grading of recommendations, assessment, development, and evaluation) process and look at more trials at the June 2013 ACIP meeting. Several options are available, and a decision is expected at that meeting.
ACIP has not evaluated the smallpox vaccine since 2003. A new smallpox vaccine (ACAM2000—Acambis) has replaced the original vaccine (Dryvax—Wyeth-Ayerst). Another smallpox vaccine (Imvamune—Bavarian Nordic) that is not licensed in the United States will be considered for inclusion in the Strategic National Stockpile.
Hepatitis A vaccine supply
The hepatitis A vaccine shortage is over. Sanofi Pasteur’s supply of Pentacel and Daptacel is low, but supply of other vaccines on the market is sufficient. Boostrix (GlaxoSmithKline) prefilled syringes are not available; however, single-dose vials are available.
General recommendations on immunizations
Updates to three sections of the general recommendations were presented. Previous recommendations in the section on timing and spacing of immunizations defined the "grace period rule" as a 4-day period in which sequential doses of the same vaccine can be given earlier than the minimum interval or minimum age. However, the grace period does not apply to the administration of two different live vaccines. This specifically applies to MMR (measles–mumps–rubella) and varicella vaccines, in that one vaccine may interfere with the other if given before 28 days. Therefore, the live vaccine rule prevents the use of the grace period rule.
Another component of the section on timing and spacing clarifies previous information regarding a slight increase in febrile seizures when influenza vaccine and PCV13 are given simultaneously (one additional occurrence per 2,200 doses given). ACIP felt that because the risk is low and the incidence of disease is high, these vaccines should be given together.
One exception to the simultaneous administration of two inactivated vaccines is MenACWY (Menactra—Sanofi Pasteur) with PCV13 in patients with asplenia, as evidence exists of interference of PCV13 response.
The section on contraindications and precautions also was revised. An issue was brought up with hospitalization for surgery and anesthesia. Concern exists regarding monitoring patients for fever after they have received a vaccine and giving bacterial vaccines before splenectomy. Also, there is some weak evidence that anesthesia decreases immunity (not to vaccination).
Another issue is the administration of vaccine to patients with a previous history of Guillain-Barré syndrome (GBS). No cases have been reported of recurrent GBS following influenza or tetanus vaccination. Therefore, this is a precaution only if the previous GBS occurred within 6 weeks of a vaccine. No contraindication to any vaccine exists if the patient has had GBS in the past.
The section on persons vaccinated outside the United States (in the special situations section) required clarification, especially regarding instances when records are not clear. Current recommendations state that self-reporting is sufficient for influenza and polysaccharide pneumococcal vaccine (PPSV). The concern is based on increased incidence of adverse effects if the interval between PPSV doses is less than 5 years. Because the number of countries that administer PPSV is low, the working group felt that self-reporting of PPSV should be dropped.
These issues surrounding general immunization recommendations only involved discussion; no voting occurred.
IOM review of childhood immunization schedule
The Institute of Medicine (IOM) was tasked to review the childhood immunization schedule and assess outcomes comparing children who did and did not follow the schedule. Also, safety was a major emphasis. IOM conducted information-gathering meetings with the public and a literature review. The following recommendations were made:
- The National Vaccine Program Office (NVPO) should assess public concerns with the goal of improving communication.
- NVPO should clarify and standardize key elements of the schedule and adverse events.
- HHS should study the safety of the schedule for epidemiology evidence, biological plausibility, and feasibility.
- HSS should not perform randomized controlled trials to compare safety for unvaccinated children due to the unethical design.
- HSS should fund and support studies of this type.
Recently, Noninfluenza Vaccination Coverage Among Adults–United States, 2011 was published. Most coverage rates only increased slightly. More needs to be done, as we are still far away from coverage goals.
In addition, the new immunizations schedules (2013) were published on January 28, 2013. Changes to the childhood schedule were minimal and included revisions in the footnotes, adding the number of doses to the schedule, and, once again, combining the childhood and adolescent schedules. Changes to the adult schedule included adding the new guidelines for Tdap and PVC13 and other small changes to format and footnotes.
Surveys were reported on physician attitudes regarding vaccination and consumer perspectives of vaccinations, as well as the CDC response to these issues. CDC is developing new education programs and tools to address concerns of consumers.
The 2012–13 influenza season arrived earlier than the previous several seasons and peaked in early January. More serious disease and deaths were seen among older individuals this flu season. A total of 145 million doses of influenza vaccine were for the 2012–13 season, 134.8 million of which have been distributed. This total is higher than that produced during the last few years, and a slight increase in demand occurred in January. Estimates of the quantity of quadrivalent vaccines for next year are not available. Supply of trivalent inactivated influenza vaccine will be adequate.
Midseason-adjusted estimates of seasonal influenza vaccine effectiveness (VE) were discussed. VE is a very complicated issue as a result of factors such as differences in immunity, circulating viruses, age, type of vaccine, and measurement of disease. The vaccine efficacy studies presented were based on very low numbers of patients (290 patients ≥65 years). Initial estimates indicate a VE of 56% and that VE differs by influenza type and patient age. For more information, see Interim Adjusted Estimates of Seasonal Influenza Vaccine Effectiveness–United States, February 2013.
New terminology for influenza vaccines has emerged. IIV (inactivated influenza vaccine) is now the preferred abbreviation, with IIV3 (i.e., vaccines that are egg based and cell culture based) replacing TIV (trivalent inactivated influenza vaccine) and IIV4 replacing QIV (quadrivalent inactivated influenza vaccine). RIV/RIV3 refers to trivalent recombinant hemagglutinin (HA) influenza vaccine (FluBlok—Protein Sciences), and LAIV/LAIV4 refers to live-attenuated influenza vaccine. Also, ccIIV or ccIIV3m refers to the cell culture–based inactivated influenza vaccine (Flucelvax—Novartis).
Quadrivalent vaccine was discussed at the previous meeting. Although more quadrivalent influenza vaccines will be available next influenza season, the supply will not be sufficient to cover everyone.
FluBlok was recently licensed in the United States for individuals 18 to 49 years of age. It is produced using insect cell culture–derived recombinant technology. The vaccine antigen is HA protein and has three times the amount of antigen as TIV. There is no egg protein; the production is high yield and takes 21 days. Clinical studies should show that the vaccine is immunogenic and safe. The manufacturer expects to produce 3 to 5 million doses for the 2013–14 influenza season. More studies are ongoing for safety and expanding age indications.
The next ACIP meeting will be June 19–20, 2013, in Atlanta, GA.
Stephan L. Foster, PharmD, FAPhA, FNAP
Professor and Vice Chair
University of Tennessee College of Pharmacy
APhA Liaison Representative to the Advisory Committee on Immunization Practices (ACIP)
CAPT (Ret) U.S. Public Health Service