CDC’s Advisory Committee on Immunization Practices (ACIP) met on October 25–26 in Atlanta to discuss the latest information on vaccines and immunization practices. ACIP voted on vaccination recommendations for herpes zoster (HZ) vaccines and mumps-containing vaccines. ACIP also voted to approve the 2018 immunization schedules and discussed updates on many other vaccine-related issues.
Following is a summary of the discussions; complete minutes of the meeting will be published on CDC’s website. ACIP’s next meeting is scheduled for February 21–22, 2018.
Preference for HZ/su vaccine over ZVL vaccine
ACIP voted to recommend the recently approved Shingrix (GlaxoSmithKline) vaccine, also known as herpes zoster subunit (HZ/su), for adults aged 50 years and older, as well as revaccination for those who previously received the Zostavax (Merck) vaccine, also known as zoster vaccine live (ZVL). ACIP voted to recommend a preference for HZ/su vaccine over the ZVL vaccine.
In discussions of the currently available HZ vaccines, ACIP addressed three policy questions:
1. Should ACIP recommend HZ/su for vaccination of immunocompetent adults aged 50 years and older?
On the basis of studies and GRADE (Grading of Recommendations, Assessment, Development and Evaluation) assessments, the workgroup determined that HZ/su is safe and efficacious and noted that there is a slight increase in local reactions compared with the ZVL vaccine. But the majority of the workgroup members said HZ/su should be recommended for those aged 50 years and older because 21% percent of HZ disease occurs in those aged 50–59 years.
2. Should individuals previously vaccinated with ZVL receive HZ/su?
On the basis of studies showing higher efficacy, significant waning of protection with ZVL, and minimal adverse reactions following vaccination of previously vaccinated individuals, the workgroup said revaccination with HZ/su should be recommended for those who previously received ZVL.
3. Should ACIP recommend a preference for HZ/su over ZVL?
Since all assumptions have demonstrated a better efficacy, duration of protection, and cost effectiveness, most of the workgroup recommended a preference for the HZ/su vaccine.
Cost-effectiveness models were presented for HZ/su, as well as comparisons of both HZ/su and ZVL with placebo among five age groups. The model assumed that HZ/su duration of protection was 20 years; however, because only 4 years of data are available, predictions of duration are difficult to make. The ZVL model assumed a 10-year duration of protection. The models projected higher rates of protection by HZ/su compared with ZVL and placebo based on several studies of vaccine effectiveness. The cost per quality-adjusted life year (QALY) for HZ/su was estimated to be $26,000–$30,000 for adults aged 50 years and older compared with $55,000–$67,000 for ZVL. It was noted that these models have many limitations, mainly because of unknown estimated variables.
On the basis of available efficacy, safety, and cost-effectiveness data, ACIP voted unanimously to recommend HZ/su for adults aged 50 years and older (15 yes votes) and to revaccinate those who have previously received the ZVL vaccine (12 yes, 3 no votes). The vote for a preference of HZ/su over ZVL was very close (8 yes, 7 no votes). Even with this narrow margin, the recommendation passed.
Approval for third dose of MMR during mumps outbreaks
ACIP voted to approve a recommendation for use of a third dose of measles–mumps–rubella (MMR) vaccine during a mumps outbreak, based on the available data.
Epidemiology of mumps cases was presented, and it was noted that mumps cases have increased yearly throughout the United States since 2013. A total of 6,366 cases were reported in 2016, and 4,677 cases were reported in 2017 through October. The highest incidence was in those aged 18–22 years, and 75% of this group had been vaccinated with two doses of the MMR vaccine. Since January 2016, 150 outbreaks have occurred, mostly in school and community settings. Thirteen percent of the outbreaks included more than 50 cases, accounting for 80% of all cases reported. The workgroup determined that this increase was not due to antigenic differences between the Jeryl Lynn vaccine strain and the circulating wild strains. Mumps complications, mostly orchitis, were seen in 2.9% (270) of all cases.
A GRADE analysis was presented on use of a third dose of MMR for outbreaks. The range of vaccine effectiveness for the third dose in three outbreaks was 61%–88%, although evidence was weak. There were no reports of serious adverse effects resulting from addition of a dose. This intervention appears to be effective, although again, the evidence is weak. A vaccine effectiveness of 88% has been established for the two-dose series, and antibodies wane over time.
Approval for 2018 adult immunization schedule
The 2018 adult immunization schedule was presented. Updates will include the changes passed at this meeting, including the preferred use of HZ/su and the MMR third dose during outbreaks. Other changes this year include HPV dose changes and removal of polysaccharide meningococcal vaccine (MPSV4), along with footnote changes. The schedule was approved and is projected to be published in early February 2018.
Approval for 2018 childhood/adolescent schedule
The 2018 childhood/adolescent schedule was presented for approval. Changes included removal of MenHibrix (Hib-MenCY) because it is no longer available, a new table listing vaccines and their brand names and abbreviations, an orange-colored box indicating precautions, and footnote changes. ACIP voted to approve the schedule.
Resources on vaccine safety: Shoulder injury after vaccination
Shoulder Injury Related to Vaccine Administration (SIRVA) increasingly is being reported. There were 2,189 Vaccine Adverse Event Reporting System (VAERS) reports of SIRVA between 2010 and 2016, of which CDC determined that 1,006 were plausible. Reports across various immunization providers indicate additional outreach should be conducted. The most commonly reported cause is injection of a vaccine too high in the shoulder, with other causes listed as improper or poor administration technique, uneven position between vaccinator and patient, needle too long, and past history of shoulder pain. CDC has developed a handout to help educate providers on correct administration of injections, as well as other resources (available at www.cdc.gov/vaccines/hcp/admin/admin-protocols.html).
Updates on influenza vaccines
The 2017 influenza recommendations were published on August 27, 2017. Since publication, one update is a licensing change for Afluria Quadrivalent (Seqirus), which lowered the approval age to 5 years and older.
The predominant influenza virus that circulated last year and is currently circulating in the Southern Hemisphere is A(H3N2). Minimal virus is circulating at this time in the United States, and most of the cases are the A(H3N2) viruses, which are a good match for the recommended vaccine strains. The new recommendation for the Southern Hemisphere vaccine for 2018 changed the A(H3N2) vaccine strain. This change was made not because of antigenic drift but because a vaccine strain was identified that better matches the circulating strain.
Vaccination coverage rates also were discussed. Data from multiple databases showed that coverage among children (69%) and adults (41.3%) increased only slightly over last year’s coverage. A slight increase was also seen in adults older than 65 years (65.3%), but the rate was still lower than in some previous years. Coverage among pregnant women was 53.6%, and overall coverage for health care providers was 78.6%. The rate for pharmacists (93.7%) was second only to that for physicians (95.8%).
Medimmune presented an update on the live attenuated influenza vaccine (LAIV) (Flumist). The company said it believes the vaccine’s reduced effectiveness in previous seasons was caused by reduced reproductive fitness of the A(H1N1) strain used. A new vaccine strain (A/Slovenia) was selected for the 2017–18 LAIV formulation. A study in ferrets—the closest animal model to humans—demonstrated a good response to the new strain. A comparative study in U.S. children will be available in December, with the goal of guiding ACIP in future evaluations.
A recent study reported an increase in spontaneous abortions (SAB) following influenza vaccination. CDC evaluated cases from the Vaccine Safety Datalink and discovered an increase in SAB in the 2010–11 season but not in 2011–12. CDC currently is evaluating three more seasons (2012–15) and expects these results by late 2018 or early 2019.
Updates on hepatitis B and A vaccines
An investigational hepatitis B vaccination (Heplisav-B—Dynavax) has been submitted to FDA for evaluation. The vaccine is an adjuvanted, recombinant hepatitis B surface antigen vaccine that is administered in two doses over a 1-month period. The adjuvant mimics natural innate immune responses to bacterial and viral DNA, which activate both B and T cell responses.
The vaccine induced higher seroprotection rates compared with the Engerix-B (GlaxoSmithKline) vaccine. It also has shown superior protection rates in all age groups, as well as in patients with diabetes, patients who are obese, and smokers. Adverse effects were similar, except that a higher incidence of myocardial infarction occurred in one of the Phase II studies; this was not seen in other studies. Overall, this vaccine appears to provide a higher rate of protection with fewer doses.
Current recommendations for hepatitis B vaccination include infants starting at birth, household contacts, those with increased sexual risks, health care workers, injection drug users, patients with diabetes, those with liver disease, and a few other indications. The incidence of hepatitis B has fallen significantly since the 1980s; however, only 41%–63% of the population who started the vaccination series received all three doses within 1 year. Limitations of the current hepatitis vaccines are that three doses are required, and effectiveness is reduced in patients with diabetes, older patients, those with renal disease, those who are immunosuppressed, and smokers. The investigational hepatitis B vaccination has potential to overcome some of these limitations.
The ACIP statement “Prevention of Hepatitis A through Active or Passive Immunization: Recommendation of the Advisory Committee on Immunization Practices,” along with other hepatitis A guidance documents, are being updated.
It was noted that five large outbreaks of hepatitis A, with approximately 1,600 cases, have occurred since July 1, 2016. California is experiencing the largest number of outbreaks, mostly in the homeless population. Additional outbreaks have been seen in Utah, Arizona, Colorado, Michigan, and New York City—again, mostly in people who are homeless and in drug users. Death rates are higher than previously reported. Past outbreaks have been reported primarily in children; however, since vaccine introduction, most are in adults. Vaccination rates of high-risk adults aged 19–49 years was 12.3% in 2015.
The current universal vaccination recommendations made in 2006 for all children have caused a significant decrease in disease. Vaccine supply for adults has been strained recently because of these outbreaks.
Update on HPV vaccine
ACIP noted that work has started on suggested wording changes for human papillomavirus (HPV) vaccine recommendations and harmonization of the upper age for male and female vaccination. The impact of the new two-dose series, the impact of HPV vaccination on disease, and vaccine safety of the 9-valent HPV vaccine will be monitored.
Updates on pneumococcal vaccine
The Georgia Emerging Infections Program performed a study to determine the extent of pediatric pneumococcal carriage following pneumococcal conjugate vaccine-13 (PCV13) vaccination. Postvaccination carriage rates of PCV13 serotypes dropped from 8/100 to less than 1/100 compared with the prevaccination carriage rate. Significant decreases in serotypes 19A and 06C were observed, as well as decreases in the other vaccine serotypes. Nonvaccine serotypes did not change, and there was no increase in any other serotype as a dominant strain.
An additional study looked at adult colonization in those who received PCV13; previous studies had shown that vaccination of children with conjugate vaccines decreases colonization of vaccine serotypes in adults but not overall colonization caused by other serotypes. This study looked for pneumococcal colonization in 3,049 adults older than 65 years who were not severely immunocompromised. Pneumococcal carriage was similar in the vaccinated (1.8%) and nonvaccinated (1.6%) groups. Vaccine-type serotype carriage also was similar (0.2% vs. 0.1%). This demonstrated that carriage in adults is rare and that PVC13 serotypes account for only 13% of those with carriage. It was postulated that the low carriage rates may be due to herd effects from childhood vaccination with PCV13. It was difficult to determine the indirect versus direct effects on adult carriage.
Invasive pneumococcal disease (IPD) rates and serotypes were reviewed for the period of 2007–16. The IPD rate decreased overall by 40%, and IPD caused by PCV13 serotypes decreased by 68%. This demonstrated significant reductions in non-PCV13 serotypes as well as PCV13-serotype IPD. There was no evidence of further reduction in PCV13-serotype IPD among adults after the introduction of PCV13 in adults in 2014. In the 6 years since PCV13 introduction in children in 2010, sustained reduction in IPD by vaccine serotypes has been seen in both children and adults. ACIP will reconsider use of PCV13 in adults in 2018. While PCV13-serotype IPD rates have declined since the introduction of vaccine in children, vaccination of adults does not appear to be changing the rates. Additional studies are under way to look at vaccine effectiveness in adults older than 65 years, PCV13 impact on community-acquired pneumonia, and cost effectiveness.
Update on Japanese encephalitis vaccine
Japanese encephalitis vaccine (JE-VC) (Ixiaro—Intercell) is the only JE vaccine available in the United States. It is currently recommended for travelers who plan to spend more than 1 month in endemic areas during the JE transmission season. It should also be considered in short-term travelers under special situations (for more information, see the CDC recommendation on the CDC website).
A total of 56 cases have been reported of traveler-associated JE worldwide since 1993, with only 12 cases in U.S. travelers during the same time period. The majority occurred during the months of June to August. Two of the U.S. patients died, and three cases survived with sequelae. Eight of the cases traveled for longer than 1 month. These data, along with assumptions of underdiagnosing, suggest the risk to be approximately one case per 1 million trips to Asia. While vaccination rates are low, JE disease is rare among travelers. Among 21,347 military personnel who received JE-VC, there was no statistically significant increase in serious adverse events compared with a previous vaccine no longer available (JE-Vax). Reports in the Vaccine Adverse Event Reporting System showed that the rates of adverse events have not increased with the introduction of JE-VC. While neurologic and hypersensitivity reactions have occurred, the rates are low (2.2/100,000 doses and 4.4/100,000 doses, respectively).
Update on anthrax
Several operational concerns were discussed about a response to a potential anthrax attack. Concerns include needle supply; confusion between two vaccines because a new vaccine, NuThrax, is expected in 2018; and issues of adherence to antibiotic therapy for 60 days plus vaccine. The workgroup will be discussing these issues over the next year.
Multiple safety studies have been performed since 2008, and no new safety signals have been discovered. One observation has been fewer local reactions with intramuscular (I.M.) administration of Anthrax Vaccine Adsorbed (AVA) compared with subcutaneous (S.C.) administration. While I.M. administration is easier, S.C. has higher titers at 4 weeks. The titers are equal to I.M. administration at 8 weeks; however, in an emergency situation, early titers are important. In addition, people don’t take their antibiotics as prescribed, putting them at an increased risk. The workgroup said it believes optimal immune response outweighs operational concerns; however, an I.M. dose should be considered valid if inadvertently given.
Update on RSV vaccine
Following disappointing results of the respiratory syncytial virus trials, the vaccine candidate is back in Phase II development.
Update on evidence-based recommendations
The GRADE Analysis process has been under consideration for improvement. The workgroup is considering replacement of the GRADE A and B recommendations to be more descriptive.