Influenza, hepatitis, HPV, and more covered at ACIP’s October meeting
Complete minutes will be available on CDC’s website
CDC’s Advisory Committee on Immunization Practices (ACIP) met in Atlanta on October 18–20 to discuss vaccine recommendations. Complete minutes of the meeting will be published on CDC’s website. Following is a summary of the committee’s discussions. ACIP’s next meeting is February 22–23, 2017.
Two new vaccines were recently licensed. Afluria Quadrivalent (QIV) by Seqirus was FDA approved in August for persons aged 18 years or older. Currently, studies are under way for persons who are older than 6 months. The trivalent (TIV) version of this vaccine has been approved for persons aged 18 years and older since 2007 and for those aged 5 years and older since 2011; however, ACIP has recommended its use for those aged 9 years and older because of reported febrile seizures in younger children. Both the QIV and TIV versions will be available this year and next, but due to manufacturing startup, most of the vaccines will be TIV this year. Only the TIV is approved for Pharmajet. In addition, Flublok Quadrivalent by Protein Sciences was approved in October.
Currently, there is little influenza activity in the northern hemisphere. The few viruses circulating are a match to the current vaccine. The predominant virus circulating is A(H3N2), but too few viruses are available to predict what will circulate this year. The A(H1N1)pdm09 virus circulating drifted slightly in the southern hemisphere this year for the first time since 2009.
In 2014, ACIP voted to add pneumococcal conjugate vaccine (PCV13) for all adults aged 65 years and older with the caveat that this recommendation should be reevaluated in 2018 and revised as needed. Current evaluation has shown a significant drop in invasive pneumococcal disease in children as well as adults since the introduction of PCV13 in children. There has been no change in non-PCV13 serotypes. From 2010 to 2015, it is estimated that PCV13 use in children has prevented 280,000 invasive pneumococcal disease cases and 20,000 deaths in all ages. This is a result of both direct vaccination effects and the indirect effects of herd immunity. There has been no evidence of serotype replacement at this time either. It appears that most of the remaining burden of invasive pneumococcal disease in adults is due to non-PCV13 serotypes. CDC revealed its research agenda, which will be ready for the 2018 report.
Respiratory syncytial virus (RSV) vaccine
RSV is a major cause of community-acquired lower respiratory tract disease in infants and children. People older than age 60 years are also regularly infected with RSV, with rates slightly lower than influenza and Streptococcus pneumonia and approximately 180,000 hospitalizations per year. Most often, RSV causes respiratory infections that are more severe than the common cold. The infection is upper respiratory for the first few days but rapidly becomes a lower respiratory tract infection, making cultures difficult to obtain. Diagnosis of RSV in children is fairly easy based on symptoms, but it is more difficult in adults because of lack of distinctive symptoms, lower fever, worsening of chronic diseases, and lower nasal shedding. Novavax has completed a Phase III trial of its vaccine in adults and is analyzing the data. Studies are continuing for maternal and pediatric immunization.
Hepatitis B vaccine
Updates to the revised statement “ACIP Recommendations for Hepatitis B Virus Infection in the United States” were reviewed. The changes were the result of incorporating recommendations by CDC and the American Association of Liver Diseases. Some of the working group changes included the following:
- Testing HBsAg-positive pregnant women for hepatitis B virus (HBV) DNA (to guide maternal antiviral therapy during pregnancy for prevention of perinatal HBV transmission)
- Postvaccination serologic testing for infants whose mothers’ HBsAg status remains unknown indefinitely (e.g., when an infant is surrendered confidentially shortly after birth)
- HBV vaccination of persons with hepatitis C virus (HCV) infection and chronic liver disease (including but not limited to those with cirrhosis, fatty liver disease, alcoholic liver disease, autoimmune hepatitis, and liver function tests greater than two times the upper limit of normal)
- HBV vaccination HBV of persons in correctional facilities
- HBV vaccination among patients on hemodialysis, determined by yearly antigen testing
A draft of the updated ACIP HBV statement was presented, and the committee voted to accept the new recommendations.
Pertussis vaccine (Tdap) in pregnancy
Pertussis incidence is still on the rise, with many outbreaks over the last 10 years. Administration of tetanus, diphtheria, and pertussis (Tdap) in pregnancy has been recommended since 2011, and the incidence of disease in the first few months of life has decreased but still persists. No safety issues have appeared in the CDC monitoring systems.
New data showed higher titers when vaccination was administered at 28 to 32 weeks’ gestation than at 33 to 36 weeks. It appears that vaccinating mothers earlier in pregnancy resulted in higher infant titers, possibly because longer exposure to the vaccine induced more antibody transferred to infants. Concerns were raised that no data are available to see if antibody titers decrease in infants if the vaccine is given too early in pregnancy. The guidelines were revised to state, “Tdap should be administered between 27–26 weeks’ gestation, although it may be given at any time during pregnancy. Currently available data suggest that vaccinating earlier in the 27- through 36-week window will maximize passive antibody transfer to the infant.”
Human papillomavirus (HPV) vaccine
Recent presentations at ACIP discussed use of a two-dose schedule of the HPV 9-valent vaccine (9vHPV, Gardasil 9—Merck) for 9- to 14-year-olds instead of the current three-dose series. While the current ACIP recommendation is for use in 10- to 11-year-olds, the vaccine can be given as early as 9 years old. On October 7, 2016, FDA approved a change in the dosing schedule of the 9vHPV label to allow for both a two-dose schedule (0 and 6–12 mo) and a three-dose schedule (0, 2, and 6 mo) for those aged 9 years to 14 years.
A summary of the evidence from previous ACIP meetings on the two-dose schedule was briefly presented. The data demonstrated a noninferiority antibody response after two doses (0 and 6 mo, or 0 and 12 mo) in 9- to 14-year-olds, compared with the standard dosing schedule of 0, 2, and 6 months in 16- to 26-year-olds. Previous studies have demonstrated high seroconversion after vaccination resulting in higher titers than natural infection, and that vaccination in younger ages results in higher antibody titers. Long-term protection data are not yet available for the two-dose schedules. The 6-month dose (booster) is very important for adequate immunological response. A minimum interval of 5 months for two doses is necessary. Memory B cells require 4 to 6 months to mature and differentiate into high-affinity B cells, and the 6-month interval allows the last dose to efficiently reactivate memory B cells.
ACIP voted to recommend a two-dose series (0 and 6–12 mo) for persons initiating vaccination before their 15th birthday and the currently recommended three-dose series (0, 1–2, and 6 mo) for persons who initiated at an older age.
HPV vaccination should be administered at age 11 or 12 years. A two-dose series, with the second dose administered 6 to 12 months after the first, may be recommended for ages 9 to 14 years. If the second dose is given before 6 months after the first, patients should receive a third dose a minimum of 6 months after the first. Persons receiving the vaccine after their 15th birthday should receive a three-dose series (0, 1–2, and 6 mo). Immunocompromised patients at any age should receive the three-dose series.
FDA approved a change to the Trumenba (MenB—Pfizer) label in April. A two-dose schedule (0 and 6 mo) was approved along with the three-dose schedule (0, 1–2, and 6 mo). According to the FDA approval, the choice depends on the risk of exposure and the patient’s susceptibility to meningococcal B disease. Data from immunological studies show similar titers and safety for the two- and three-dose schedules. Current ACIP recommendations state that either meningococcal vaccine should be given to all persons over the age of 10 years who are at increased risk (Category A) and may be administered to adolescents on the basis of clinician judgment (category B).
A study was recently performed to determine meningococcal B carriage in an outbreak at a college in Rhode Island. It is known that meningococcal serogroup C and A vaccines reduce carriage, but serogroup B vaccination reduction of carriage is not known. Trumenba was administered during a meningococcal B outbreak, and pre- and postvaccination oropharyngeal swabs were obtained. Results demonstrated that 20% to 24% of participants (n = 622–878, depending on number of doses received) carried meningococcal bacteria, with 4% carrying serogroup type B. Despite high carriage, only one carrier of outbreak strain was found. Vaccination did not appear to affect carriage. Also, persistence studies showed that while there is a decrease in titers over time, titers persist for at least 4 years.
Herpes zoster vaccine
The current ACIP recommended vaccine for herpes zoster is Zostavax (Merck), given as a single dose for all individuals aged 60 years and older. Efficacy is 51% against herpes zoster disease and 67% against postherpetic neuropathy; however, waning of immunity occurs after 7 to 8 years. Vaccine uptake is sluggish, with several factors affecting rates (i.e., price, must be frozen, Medicare Part D, low prioritization of adult vaccines, fragmented care for seniors). Several new zoster vaccines are in Phase III trials.
An investigational vaccine by GlaxoSmithKline known as HZ/su was first presented to ACIP in June 2015. This adjuvanted, inactivated vaccine is administered in a two-dose series (2 mo apart). In a study, efficacy in patients older than age 50 years was 97.2%. An additional study of patients older than age 70 years showed vaccine efficacy of 89.9% in this age group. The vaccine is very reactogenic, with adverse reactions reported in 79% of the patients. More studies are planned, with potential FDA submission for approval by the end of 2016.
Yellow fever vaccine
Stockpiles of yellow fever vaccine have been depleted because of outbreaks in Africa. This is expected to continue through 2016.
A total of 3,808 cases of Zika virus have been reported in the United States, with most being imported. There is an active area in Miami, FL, where pregnant women should not travel.
The new childhood schedule was presented. Multiple footnote changes have occurred to reflect changes over the last year. A new high-risk table has been added to indicate who should be vaccinated when they have select medical conditions. Other changes include a title change, addition of a 16-year-old column, and removal of live attenuated influenza vaccine (LAIV) recommendation. The committee voted to accept the new schedule.
The 2017 adult schedule was presented. Again, there were multiple footnote changes, along with a title change, changes to contraindications, and several format changes. The committee voted to accept the new schedule.