October Updates from Advisory Committee on Immunization Practices
Oct 26, 2016
Last week, the Advisory Committee on Immunization Practices (ACIP) held it’s third and final meeting of 2016. The agenda included presentations pertaining to hepatitis B, pertussis, HPV, meningococcal, herpes zoster, pneumococcal and RSV vaccines, and surveillance updates on Zika and influenza viruses.
During the two-day meeting, the committee took nine votes on newly proposed vaccine recommendations that addressed vaccination timing, number of doses needed, and dosing intervals for hepatitis B, pertussis, HPV and meningococcal vaccines. They also approved the child, adolescent and adult immunization schedules.
This post provides a recap of each agenda item in the order they occurred.
Hepatitis B Vaccine
The recommended first dose of the three-series hepatitis B vaccine is often referred to as “birth dose” and is typically administered to infants in the hospital after birth. At this meeting, the Hepatitis B Work Group asked that the Committee consider removal of the permissive language that appears at the end of the recommendation which allows for a delay of the birth dose until after hospital discharge.
When hepatitis B vaccine is administered within 24 hours of birth it can help prevent transmission of the hepatitis B virus from an infected mother to her child. The intent of the birth dose is to provide an additional safety net to prevent transmission from HepB positive mothers that are not properly identified due to errors in maternal testing or reporting. In these instances, when the mother is not properly identified as HepB positive before birth, the HepB vaccine alone is 75% effective in preventing prenatal transmission, and 94% effective when used in conjunction with Hepatitis B immune globulin.
Since delaying hepatitis B vaccination can interfere with the prevention of Hepatitis B – especially in a child unknowingly born to a HepB positive mother – the HepB Work Group proposed that the reference to delaying vaccination be removed from the recommendation. It had originally been added in 2005, but the data suggests that administering the birth dose in the hospital leads to timely completion of the series. The current birth dose coverage was stated to be 72.4% of children, which remains below the Healthy People 2020 goal of 84%.
The Committee voted to remove the permissive language as well as include new language to clarify that the first dose of vaccine should be administered within 24 hours of birth, which is more explicit than “before hospital discharge”.
The anticipated changes to the previous recommendation are indicated below, however the exact wording may differ once published by the CDC:
“For all medically stable infants weighing 2,000 grams or more at birth and born to HBsAg-negative mothers, the first dose of vaccine should be administered
before hospital dischargewithin 24 hours of birth. Only single antigen HepB vaccine should be used for the birth dose. On a case-by-case basis and only in rare circumstances, the first dose may be delayed until after hospital discharge for an infant who weighs 2,000 grams or more and whose mother is HBsAG-negative”.
*It should be noted that for those infants with birth weight of less than 2,000 grams, the birth dose is not counted as part of the vaccine series.
There was some discussion concerning the removal of the option to delay vaccination and it was emphasized that having a clear recommendation from the ACIP is not a vaccine mandate. Rather, practitioners, public health professionals and parents rely on the ACIP recommendations as expert guidance and best practice. The Hepatitis B “birth dose” has been a successful strategy to help eliminate hepatitis B virus transmission in the U.S., and the ACIP’s revised recommendations only emphasize the importance of vaccinating within the 24 hours timeframe that will help prevent further transmission.
Other key updates to the hepatitis B vaccine recommendations included:
- Providing examples of chronic liver disease, including recommending HepB vaccine for persons with HCV infection.
- Post vaccination serologic testing for infants who’s mother’s HBsAg status remains unknown indefinitely.
- Testing HBsAg-positive pregnant women for HBV DNA.
For more information as to why babies need a Hepatitis B vaccine at birth, read these Shot of Prevention blog posts here.
The Committee reviewed the history of Tdap vaccination in pregnant women and reviewed studies that found that maternal Tdap vaccination to both safe and effective at preventing infant pertussis.
The session began with the Pertussis Work Group presenting a detailed report of the epidemiology of pertussis and a thorough review of safety data and studies. One study included more than 50,000 women who received Tdap vaccine during pregnancy which showed no increased risk for adverse maternal or infant health outcomes. Another study demonstrated vaccine safety among pregnant women who had received a repeated Tdap dose. The Committee also reviewed data that correlated the timing of Tdap vaccination with cord blood antibody levels.
To summarize, the immunogenicity studies confirmed that infants of Tdap vaccinated mothers were born with significantly higher anti-pertussis antibodies compared to infants of unvaccinated mothers. In fact, studies showed that the maternal Tdap vaccine was 78-93% effective at preventing infant pertussis infection.
Additionally, their review of the studies showed that maternal Tdap is also effective at reducing the severity of pertussis infection. For example, infants who did contract pertussis were older, had a lower risk of hospitalization and ICU admittance, and no deaths, if born to a mother who was vaccinated in pregnancy.
During this extensive review and discussion of the immunogenicity, efficacy and programmatic considerations of Tdap administration during pregnancy, the most critical discussion point occurred when reviewing studies pertaining to the timing of maternal vaccination.
In evaluating the current vaccine recommendation “window” of 27-36 week administration, studies revealed that the concentration of anti-pertussis antibodies in infant cord blood was higher when mothers were vaccinated earlier. It appears that the mother is able to produce higher vaccine induced antibody levels when vaccinated earlier in pregnancy. In fact, the infant cord blood concentration of anti-pertussis antibodies was similarly high when maternal Tdap vaccine was administered before 27 weeks.
While this was a notable discovery, the Committee was careful not to equate higher concentration from earlier vaccination to better effectiveness in protecting the infant after birth. Without access to further studies it would be difficult to know whether the durability and concentration of maternal antibodies would be maintained and sustained through the infant’s first DTaP dose at 2 months of age. Without effectiveness data that is specific to vaccinating women earlier, the Committee remained cautious not to “over-interpret” the results from the current studies.
The Committee then moved to discuss various options that would allow them to retain the current window of 27-36 weeks, while also accounting for the data showing the best transfer of immunity is occurring earlier in the 3rd trimester, specifically between 27 and 32 weeks. Various programmatic considerations were discussed at length and in the end, a vote was taken to modify the recommended language for maternal Tdap vaccination as follows:
“Tdap should be administered between 27 and 36 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.”
To learn more about the importance of pertussis vaccination in pregnancy, visit the pregnancy section of our Vaccinate Your Family website here.
Human Papillomavirus (HPV) Vaccines
Following FDA approval on October 7, 2016 of a 2-dose series of the 9-valent HPV vaccine for those age 9-14 years of age, the ACIP was poised to vote on a change in their HPV recommendations. The ACIP has been preparing for this by reviewing data related to 2-dose schedules, including immunogencity, post hoc analyses of efficacy trials, post-licensure effectiveness, health economic models and duration of protection all throughout the year.
Studies show that the antibody response after 2 doses of HPV vaccine (0, 6 months, or 0, 12 months) in 9-14 year olds is non-inferior to the response after 3 doses in the groups in which efficacy was demonstrated. Data from the follow-up immunogenicity trials suggest duration of protection will be the same after a 2-dose schedule as is expected for a 3-dose schedule. Based on a thorough review of all the available data, the HPV Vaccines Work Group proposed a recommendation for a 2 dose schedule for persons initiating the series at 9 through 14 years of age.
A vote was taken to approve the following dosing schedule:
- For persons initiating vaccination before the 15th birthday, the recommended immunization schedule is 2 doses of HPV vaccine. The second dose should be administered 6-12 months after the first dose (0, 6-12 month schedule).
- For persons initiating vaccination on or after the 15th birthday, the recommended immunization schedule is 3 doses of HPV vaccine. The second dose should be administered 1-2 months after the first dose and the third dose should be administered 6 months after the first dose (0, 1-2, 6 month schedule).
- Persons who initiated vaccination with 9vHPV, 4vHPV or 2vHPV before the 15th birthday, and received 2 doses at the recommended dosing schedule, or 3 doses at the recommended dosing schedule, are considered adequately vaccinated.
- Persons who initiated vaccination with 9vHPV, 4vHPV or 2vHPV on or after the 15th birthday, and received 3 doses at the recommended dosing schedule, are considered adequately vaccinated.
- 9vHPV will be the only vaccine available after 2016 and may be used to continue or complete a series started with 4vHPV or 2vHPV.
- For persons who have been adequately vaccinated with 2vHPV or 4vHPV, there is no ACIP recommendation for additional vaccination with 9vHPV.
- If the vaccine schedule is interrupted, the vaccination series does not need to be restarted.
- Number of recommended doses is based on age at administration of the first dose.
- Three doses are recommended for people with weakened immune systems aged 9-26 years.
* Additional recommendations were made, as is customary, for specific medical conditions and lifestyles, which will be noted in the footnotes of the official schedule.
It should be noted that Dr. Paul Offit made a public comment of concern that the ACIP still considers a full series of either 2vHPV or 4vHPV to be adequate since they are not recommending that these persons receive additional vaccination with the 9vHPV vaccine. He stated that if the ACIP would recommend two doses of 9vHPV for those who have completed a series with either 2vHPV or 4vHPV, we could potentially prevent another 3,000 cases of cancer and hundreds of deaths. He questioned whether this was a programmatic or financial decision, and asked that the Work Group take this into consideration in the future.
It is the hope that the new 2-dose schedule will help facilitate greater vaccine initiation and series completion in the U.S. Generally, the idea of a 2-dose schedule, with the second dose following within 6-12 months of the first dose, is expected to be easier to implement, and will allow flexibility as vaccinations could coincide with preventive health care visits.
For more information about why parents should consider the HPV vaccination for their children, read one of Shot of Prevention’s most popular HPV blog posts here.
In addition, the CDC’s Immunization Services Division is providing guidance about the new HPV vaccine recommendations to parents, healthcare professionals, and insurers by hosting a one-hour webinar on October 26 at 12:00 p.m. (ET) with Dr. Lauri Markowitz of the Division of Viral Diseases. Registration is now open here. If you are unable to participate, it will be posted on CDC’s Current Issues in Immunization website after November 1 and Continuing Education credits will continue to be available for 30 days.
Meningococcal B Vaccine
The committee discussed and voted to approve a revised dosing schedule for one of the two meningococcal serogroup B vaccines licensed in the U.S. for those aged 10-25 years of age.
Since October, 2014, MenB-FHbp, which is also known as Pfizer’s Trumenba vaccine, has been administered in three doses to help prevent serogroup B meningococcal disease. Another serogroup B meningococcal vaccine, MenB-4C, also known as GlaxoSmithKline’s Bexsero vaccine, has been administered in two doses since it became available January 2015.
On April 14, 2016, the FDA approved a change to the dosing and administration of Trumenba, prompting the ACIP to consider updating it’s dosing language.
The current ACIP recommendation for Serogroup B Meningococcal (MenB) vaccines is as follows:
“Certain persons age 10 and older who are at increased risk for meningococcal disease should receive the MenB vaccine (Category A recommendation).
A MenB vaccines series may be administered to adolescents and young adults aged 16-23 years to provide short-term protection against most strains of serogroup B meningococcal disease (Category B).”
In evaluating the short-term immunogenicity of the vaccine in question, the Work Group presented evidence that the 0, 6 month 2-dose schedule evaluated for MenB-FHbp had the highest percentage of responders and is most similar to a 3-dose schedule. However, they also found that the proportion of subjects with composite response to the four primary strains is slighter lower with a 2-dose schedule compared to a 3-dose schedule, and the titers were lower with a 2-dose schedule when compared to either 3-dose schedule.
This adds to the general understanding that the vaccine impact of meningococcal carriage is limited for MenB vaccines. After vaccination, titers can decline quickly, especially for strains with low antigen expression.
The Committee agreed that the best way to proceed was to present a choice in dosing schedule which is driven by the patient’s risk of exposure and susceptibility to meningococcal serogroup B disease.
For persons at increased risk for meningococcal disease and persons susceptible during a serogroup b outbreak, the Committee voted to retain the 3 dose schedule of of MenB-FHbp (Trumenba) but administer the doses at 0, 1-2, 6 months, as opposed to 0, 2 and 6 months.
However, when given to healthy adolescents who are not at increased risk for meningococcal disease, the Committee voted to change the recommendation to 2 doses of menB-FHbp administered at 0 and 6 months. The new recommendation states that if the second dose is given at an interval of less than 6 months, a third dose should be given at least 6 months after the first dose.
The Work Group will continue to review new data on MenB vaccines as it becomes available and will consider booster doses of MenB vaccine for persons at increased risk if it is deemed necessary.
For more information about the various vaccines that protect adolescents against meningococcal disease, visit the PreTeen and Teen pages of the Vaccinate Your Family website here.
Herpes Zoster (Shingles) Vaccine
The ACIP received an update on herpes zoster epidemiology and vaccine coverage noting that the epidemiology of herpes zoster virus (also known as shingles) is changing and there is not yet a full understanding of the reasons why.
At this time it appears that vaccines to prevent both varicella and shingles are reducing the amount of circulating disease in the population. However, the overall lifetime risk of developing shingles is about 32%, with the risk increasing with age. Unfortunately, only 28% of adults 60 years of age and older have received the current herpes zoster vaccine, Zostavax, as recommended.
The Committee has been reviewing two new promising herpes zoster vaccines that are currently in phase III clinical trials. At this meeting, the Committee received an update on the phase III study of Shingrix from Glaxo Smith Kline (GSK), and the data was encouraging. It appears that Shingrix will reduce the risk of shingles by about 88%, even in the fourth year after vaccination, which is an improvement over the current Zostavax vaccine which reduces the risk of shingles by 70% but wanes quickly, especially in older recipients.
While Zostavax is already approved for those 50 and older, the ACIP recommendation suggests vaccination begin at age 60, due to the higher risk of disease in those 60+ and the waning protection offered by the vaccine. Yesterday, GSK submitted a request for licensure of Shingrix to the FDA and is seeking approval for the vaccine to be administered to people 50 years of age and older. Even if the FDA approves the vaccine for use in those 50 and older, that does not mean the ACIP will vote to recommend it for people beginning at that age, but with improved longevity of protection it could be a consideration.
Additionally, because Shingrix is made of a protein from the surface of the varicella zoster virus, and not a live version of the virus, GSK is also testing it in patients with blood cancers, HIV and transplant patients, to find out whether it can protect people with compromised immune systems. These individuals are typically at increased risk of suffering with shingles, but they can not generally receive live vaccines like the current herpes zoster vaccine Zostavax. If the vaccine is determined to be safe and effective for this high-risk population that would be a significant benefit to those individuals.
The Committee will continue to monitor the data from the phase III trials of both of the two new vaccines and anticipates further discussion if FDA approval is obtained.
To read more about shingles and the vaccines to help prevent it, read “Preventing Shingles Today and the Promise of a New Vaccines Tomorrow” on our Shot of Prevention blog.
Zika Virus Update
The Committee received an update on Zika virus transmission, a virus that was first isolated from a monkey in 1947 but did not cause human disease outbreaks until 2007. Throughout 2015 and through October 2016 there have been reports of 3,892 travel associated cases and 25,999 locally acquired cases in the U.S., mainly detected in Puerto Rico. As of October 17, 2016, there were 160 locally acquired cases reported by Florida Department of Health. However, it is also suspected that since many cases are asymptomatic, that there is roughly 30% underreporting of cases.
The goal is to have one or more candidate vaccines available in the U.S. by 2018 for emergency use in high risk populations. Currently, there are several vaccines in pre-clinical development and four vaccines in phase I clinical trials that will move to phase II trials in early 2017. The Committee will conduct a thorough session on Zika vaccines during the February, 2017 meeting.
To learn more about the Zika Virus, visit the CDC website here.
Reports to the Committee have shown that pneumococcal vaccines have been responsible for significant decreases in overall cases of invasive pneumococcal disease among children and adults. We have seen significant reductions in PCV13-type invasive pneumococcal disease following the first five years of PCV13 use, with no significant changes in non-PCV13 types among children and adults. In 2010-2015, PCV13 use in children has prevented an estimated 280,000 cases and 20,000 deaths among all ages. Specifically, in kids under the age of 5, the disease has been reduced from 100 cases per 100,000 to only 9 cases per 100,000 since 2007.
Back in August of 2014, the Work Group concluded that in the short-term, the recommendation for universal PCV13 use was warranted. However, because expected cases have been prevented from indirect effects of herd immunity, as well as direct effects of vaccination, the Work Group will continue to evaluate whether these effects may limit the utility of a universal recommendation long-term.
The season is just getting started, but based upon 1,000 isolates in the U.S. so far, it appears that the predominant strain is influenza A H3N2.
For the 2016-2017 season, the flu vaccine will protect against the influenza viruses that researchers predict will be most common during the season. This includes an influenza A (H1N1) virus, an influenza A (H3N2) virus, and one or two influenza B viruses, depending on whether the flu vaccine is trivalent (which protects against three flu viruses) or quadrivalent (which protects against four flu viruses). Both the trivalent and quadrivalent flu vaccines are available in the U.S this season, with an estimate of 168 million doses of flu vaccine in total, with 96 million doses being of the quadrivalent type.
This season the CDC recommends use of injectable/inactivated flu vaccines (or IIV) or the recombinant influenza vaccine (RIV). However, since the nasal spray flu vaccine (live attenuated influenza vaccine or LAIV) was found to be ineffective against strains in recent years, it is recommended that this vaccine should not be used during the 2016-2017 season.
Currently there is still low activity and no mortality yet this season but the Committee will receive updates at the next ACIP meeting in February 2017.
Respiratory Syncytial Virus (RSV)
The RSV Working Group was convened to evaluate vaccine use in adults 60 and older, and adults with underlying medical conditions. On September 15, 2016 Novavax released results of their phase III clinical trial and then presented their conclusions to the Committee at this meeting. While the trials were not as promising with regard to effectiveness of the vaccine, the company stated that they are committed to further development for older adults. Phase III trials of a maternal RSV program are underway with support from the Bill & Melinda Gates Foundation. This vaccine would be given to pregnant women to reduce transmission of the virus among newborns, who are especially vulnerable to RSV.
In addition to specific vaccine recommendations, the Committee also voted to approve several modifications to the 2017 child, adolescent and adult immunization schedules which will allow for ease of use. Votes were also taken to align the new recommendations for hepatitis B, HPV, and meningoccocal serogroup B vaccines to the Vaccines For Children program.
In conclusion, please note that the live-meeting archives for past ACIP meetings, as well as the printed minutes and presentation slides will be posted on the CDC website within the next few weeks.
Additionally, The National Foundation for Infectious Diseases (NFID) will be hosting a webinar on November 16th from 1-2 pm EST to discuss the updates from the October 2016 ACIP meeting and explain how these recent changes will impact vaccination programs. The webinar will be conducted by William Schaffner, MD, NFID Medical Director and NFID liaison to the ACIP, in conjunction with NFID Secretary, Patricia Stinchfield, MS, CPNP, CIC, Senior Director, Infection Prevention & Control and Pediatric Nurse Practitioner, Infectious Disease/Immunology at Children’s Minnesota and current liaison member to ACIP. To register, visit the NFID site here.
The next meeting of the ACIP is schedule for February, 2017. Subscribe to Shot of Prevention to ensure you receive all the latest vaccination news and ACIP updates.
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