ACIP’s February meeting focused on influenza, hepatitis, HPV, and more
Next meeting scheduled for June 20–21, 2018
CDC’s Advisory Committee on Immunization Practices (ACIP) met in Atlanta on February 21–22, 2018, to discuss a variety of immunization topics, including influenza activity and use of the live attenuated influenza vaccine (LAIV) in the upcoming season, hepatitis B and A recommendations, and an update on the human papilloma vaccine (HPV). A summary of these discussions is presented here, and complete meeting minutes will be published on CDC’s website. The next ACIP meeting is scheduled for June 20–21, 2018.
The number of influenza cases is starting to decline for this season, but activity is still widespread. This season marks the highest rate of hospitalizations since 2009. Eighty-nine percent of type A viruses have been the H3N2 strain; however, type B virus cases are increasing. The committee noted that 98% of the H3N2 component was a match to the cell-propagated vaccine, but only 64% matched the egg-propagated vaccine virus. In addition, the B viruses have had minimal drift this year (<1%).
Interim overall vaccine effectiveness (VE) against medically attended influenza through February 3, 2018, was 36% with a VE of 24% against A(H3N2), 67% against A(H1N1), and 42% against type B. These rates all varied by age, and a final report on VE will be presented at the end of the flu season. Studies are ongoing to look at cell- versus egg-propagated vaccine and the effects of previous infection or vaccination on immune response to vaccination. Vaccine virus selection by the World Health Organization (WHO) was released on February 22, 2018, with WHO recommending a change in next year’s A/H3N2 and B Victoria vaccine strains. At that time, WHO said the strain selection for the United States would be discussed over the next few weeks.
A new LAIV vaccine strain (type A/Slovenia) against A/H1N1 was selected and compared to the less-effective strain used before the removal of the recommendation for LAIV use. It was discovered that the decrease in effectiveness was probably a result of poor virus replication. The A/Slovenia strain demonstrated higher seroconversion rates than the older A/Bolivia strain. The conversion rates were also higher in patients with no prior exposure to influenza disease or vaccination. Replication in human nasal cells may have been decreased with the A/Bolivia vaccine strain. New methods of testing for this potential problem will be used in the future for vaccine strain selection.
The new LAIV virus VE will not be known until it is studied during a H1N1 season. ACIP committee members had diverse opinions about returning a recommendation for use of LAIV. They acknowledged that many pediatric deaths and hospitalizations have occurred in unimmunized children, the vaccine is safe, and lack of LAIV has decreased vaccination rates in certain locations, such as school programs. However, the overall vaccination rate has not decreased since LAIV was withdrawn. At the same time, they are concerned about returning a vaccine to be extensively used that has not been proven to be effective.
Other injectable vaccines have not been evaluated for effectiveness individually, and some committee members said that the nasal LAIV (Flumist Quadrivalent—AstraZeneca) should not be singled out. Also, VE varies by season, and most new vaccine approvals are based on immunogenicity data. Some committee members also pointed out that if LAIV is not reintroduced, the vaccines may be removed from the market.
ACIP members voted for the following recommendation:
“For the 2018–2019 season, immunization providers may choose to administer any licensed, age- appropriate influenza vaccine (including LAIV, inactivated influenza vaccine [IIV], and recombinant influenza vaccine [RIV]). The quadrivalent LAIV is as an option for influenza vaccination for persons for whom it is otherwise appropriate.”
An efficacy study was presented on use of Fluarix Quadrivalent (GlaxoSmithKline) in children aged 6 months to 35 months. It was recently approved by FDA for persons aged 6 months and older. Flulaval (GlaxoSmithKline) and Fluzone (Sanofi-Pasteur) influenza vaccines are already approved for this age group. ACIP voted to recommend Fluarix for this age group.
Hepatitis B and A vaccines
Heplisav-B (Dynavax), an adjuvanted hepatitis B vaccine administered as a two-dose series separated by 1 month, was licensed by FDA on November 9, 2017. A GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) analysis demonstrated that it was safe and effective compared with Engerix B (GlaxoSmithKline). Engerix B (Merck) and Recombivax B (Merck) are used in a three-dose series over 6 months.
There is evidence that Heplisav-B demonstrates a higher rate of seroprotection compared with the other vaccines, especially in population groups that do not respond as well to the current vaccines. Some safety concerns about this vaccine, such as a slight increase in cardiovascular events, will be further assessed in postmarketing studies. The ACIP workgroup does not recommend starting the series with one vaccine and completing it with the other. Future ongoing studies will be presented for use of this vaccine in special populations, along with cost-effectiveness studies. The committee voted to recommend the Heplisav-B vaccine for use in persons aged 18 years and older for protection against hepatitis B infection. No preference was stated for this vaccine versus the others.
Multiple hepatitis A outbreaks have been reported recently. A GRADE analysis was presented to evaluate the data on use of the vaccine for postexposure prophylaxis (PEP) against hepatitis A infection in persons older than 40 years of age. Only one study was identified comparing hepatitis A and immune globulin (IG), and only one immunogenicity study was identified in adults older than 40 years of age.
The hepatitis A vaccine has been recommended for PEP for healthy persons aged 40 years and younger. Those older than 40, however, need both the hepatitis A vaccine and IG. ACIP noted that PEP is difficult with IG now because the amount of hepatitis A antibodies in IG is low as a result of declining titers in donors. This led to a recent recommendation for use of a higher dose of IG, which in turn resulted in difficulty obtaining IG and an increase in its cost.
Vaccine alone is currently being recommended in some states as well as other countries; however, limited data are available in adults older than 50 years. ACIP members said they believe the vaccine should be administered to all ages and that IG should continue to be recommended in those older than 40 years if it is available within 14 days of exposure. Other issues to be discussed in future meetings include PEP of hepatitis A in immunocompromised and pregnant women.
The wording of the final vote was as follows:
- Hepatitis vaccines should be administered for PEP for all persons older than 12 months. In addition to hepatitis A vaccines, IG may be administered to persons older than 40 years depending on the providers’ risk assessment. This recommendation passed.
- Hepatitis A vaccine should be administered to infants aged 6 months to 11 months traveling outside the United States when protection against A is recommended. This recommendation also passed. The table summarizes the current recommendations.
Twenty-nine million doses of 9-valent HPV have been distributed in the United States. A review of the safety data for 9vHPV showed the most frequently reported adverse drug events were dizziness, syncope, headache, and injection site reactions. No serious safety signals were identified through the Vaccine Adverse Event Reporting System (VAERS), and the safety profile appears to be consistent with prelicensed trials.
Currently, the recommended schedules for males and females are different. The HPV vaccine is recommended for women aged 9 through 26 years and males aged 9 through 21 years, with a permissive recommendation for males aged 22 to 26 years. Harmonization of upper age recommendations for males and females would simplify the schedule and facilitate reaching high-risk males who are currently in the 22- to 26-year high-risk recommendation age but are not getting the vaccine because of confusion. A future review of cost effectiveness and additional evidence will lead to a potential vote later this year.
HPV-related cancers are observed in the cervix, oropharynx, vulva, vagina, penis, and anus. A total of 34,864 cases of HPV-related cancers have been diagnosed annually from 1999 to 2014. Overall, HPV-related cancer rates have increased during this time period, while cervical cancer rates have decreased. Oropharyngeal cancer in males is the most common and is increasing. One trial has shown that vaccination has resulted in a reduction against oral HPV infection. Since screening for oral HPV is not currently feasible, vaccination is the most promising intervention available.
ACIP must decide this year if use of pneumococcal conjugate vaccine-13 (PCV13) in adults aged 65 years and older should be continued. While efficacy of PCV13 against invasive pneumococcal disease (IPD) and pneumonia was proven in the CAPITA trial, the VE when used alone or with the pneumococcal polysaccharide vaccine-23 (PPSV23) is not known. Two case-controlled trials showed that PCV13 was moderately effective in preventing IPD; however, a slightly lower VE (i.e., 36%–65% in the case-control trial vs. 75% in CAPITA) was seen. The study was unable to evaluate VE for PPSV23 or the combination.
Several models were developed to determine the direct versus indirect (herd) effects of PCV13 vaccination in adults. These models demonstrated limited indirect or direct effects of PCV13 vaccination on IPD caused by PCV13 serotypes. Data collection and analysis continue. A Pfizer-sponsored study showed a VE of 73% against hospitalized, vaccine-type community acquired pneumonia (CAP), which causes about 3% to 5% of all CAP cases in unvaccinated adults.
What has been determined up to this point is that
- Pneumococcal carriage among adults aged 65 years and older is very low.
- PCV13 coverage among adults aged 65 years and older is approximately 40%.
- Vaccine-type IPD had declined in all age groups and plateaued in 2014-16.
- Models on the direct and indirect effects show that very few cases were prevented.
Future presentations will include continued updates about PCV13 impact on pneumonia, cost effectiveness, and public health impact.
Since the introduction of the meningococcal ACWY (menACWY) conjugate vaccines, the incidence of meningococcal disease has declined 10-fold. Now serogroup B is the primary cause of disease. In 2015, ACIP recommended that meningococcal B vaccine may be used in adolescents and young adults. Even though the incidence of meningococcal type B disease is low, the incidence of disease in college students (average 20 cases/ y) is slightly higher than that in noncollege students (average 9/y). The incidence of types C,W,Y is lower than type B and is similar in both college students and noncollege students because of the success of the menACWY vaccination program.
Vaccination during outbreaks in universities has been challenging, with fewer than 60% receiving the first dose and even fewer the second and third doses. Evaluation of current data has shown that the number needed to vaccinate or treat (NNT) to prevent one case of meningococcal type B disease in college students is 305,000, and the NNT to prevent one death is 2,765,000. There is evidence that protection starts to wane as early as 12 months following completion of the series. Currently, there is no proposal by the workgroup to change the recommendations.
The anthrax vaccine is licensed for both IM (preexposure prophylaxis) and SC (postexposure prophylaxis) uses. When the demand for the anthrax vaccine exceeds supply, as in a mass exposure, SC administration would be dose-sparing. ACIP addressed the concerns about confusion with the two formulations of the vaccine and two routes of administration (SC in adults and IM in children). The committee also noted that there are fewer local adverse events with IM administration; however, the SC administration causes higher titers at 4 weeks. ACIP will hold more discussions about the anthrax vaccines future meetings so an ACIP recommendation can be made.
Japanese encephalitis vaccine
Japanese encephalitis (JE) infection, which is endemic to Asia and the Western Pacific, is usually asymptomatic. However, when it occurs, clinical disease is severe, with significant mortality and morbidity. The risk of disease in travelers is very low, with an incidence in the United States of approximately one case per year. The only vaccine available in the United States for JE infection is Ixiaro (Intercell), which costs approximately $600 for the two-dose series. ACIP recommends the vaccine for those who plan to spend a month or longer in an endemic area during JE season or are traveling to high-risk endemic areas. It is not recommended for short-term travelers in urban areas or outside the JE season. The workgroup will address recommendations, safety, and cost effectiveness as more data become available.
The National Center for Emerging and Zoonotic Infectious Disease, a CDC branch, is developing a national plan to address prevention of health care–associated infections. This plan would include recommendations for potential vaccines (such as Staphylococcus and Clostridium vaccines that are under development), monoclonal antibodies, antibiotic resistance issues, and other related interventions. Discussion is under way about the need for a new ACIP workgroup.