Below are the key highlights:
· The ACIP and AAP are advising against using LAIV (FluMist®) for the 2016-17 season
· Newly licensed influenza vaccines include FLUCELVAX® quadrivalent for persons > 4 years and Fluzone® Southern hemisphere vaccine for use in the U.S.
· Meningococcal ACWY vaccine is recommended for use in HIV-infected persons
· Cholera vaccine (Vaxchora®) is recommended for use in adult travelers to areas of active cholera transmission
· Evidence was presented for potential future recommendations including: An expanded age indication down to 6 months for FLULAVAL®, a 2-dose HPV series, and a 2-dose schedule for Meningococcal B vaccine: Trumenba®
In light of the evidence of poor effectiveness of LAIV (FluMist) in the U.S. over the last several influenza seasons, ACIP has made the interim recommendation for the 2016-17 season that LAIV should not be used. An interim recommendation is valid for this season, but it does not mean that the recommendation will necessarily be the same next season.
The American Academy of Pediatrics (AAP) Committee on Infectious Diseases (COID) reviewed the vaccine effectiveness evidence and came to the same conclusion as the ACIP, and will also recommend that children not receive LAIV this season.
The FDA is reviewing data and is working with AstraZeneca concerning the post-licensure effectiveness data, which they asked for when approving the LAIV quadrivalent formulation. That being said, the FDA is not making any decisions concerning licensure at this point.
Because of this vote that LAIV not be used, insurance companies are not obligated (by ACA rules) to cover this vaccine. Patients may find that their insurance plans may or may not cover LAIV.
The issue around LAIV has nothing to do with safety, only lack of clinical effectiveness of the vaccine. The evidence that was examined came from the CDC's Vaccine Effectiveness (VE) network. It showed that in the 2015-16 season for ages 2-17 years, injectable inactivated influenza vaccine IIV3/IIV4 had a vaccine effectiveness of 63% for all subtypes of influenza combined compared to an effectiveness of 3% for LAIV. The key concern is lack of effectiveness against A:H1N1 pandemic type of influenza. In terms of relative effectiveness, a child age 2-17 years who received a LAIV vaccine was 2.63 times more likely to contract laboratory confirmed influenza than a child who received an injectable vaccine.
This apparent lack of effectiveness came even after MedImmune had reformulated LAIV (FluMist) using a new H1N1 seed strain intended to deal with the heat instability of the vaccine that was presumed to be the cause of lower effectiveness compared to injectable vaccine in prior seasons. It is speculated that lack of performance may be tied somehow to the quadrivalent version of the LAIV vaccine, as comparative trials using the trivalent LAIV did not show this low level of effectiveness. Those trials with trivalent LAIV were also performed prior to the emergence of the 2009 pandemic H1N1 strain. The earlier trials were also conducted in a population with lower prevalence of previous influenza vaccination. Some have speculated that prior immunization may play a role in immunogenic response to a vaccine delivered through the nasopharynx.
AstraZeneca (MedImmune) has been conducting post-licensure trials as requested by the FDA, and their data shows a level of effectiveness of LAIV that is greater than the level seen in the CDC's data, although the IIV vaccines appear to be more effective than LAIV quadrivalent in the AstraZenica study data as well.
The ACIP voted to remove LAIV from the Vaccines for Children (VFC) program for the 2016-17 season.
Newly licensed influenza vaccines include FLUCELVAX® quadrivalent for persons > 4 years and Fluzone® southern hemisphere vaccine for use in the U.S. to be given to travelers to the southern hemisphere during their influenza season.
Meningococcal Conjugate 4-Valent (ACWY) Vaccine: MCV4
Due to studies showing that the risk of contracting meningococcal disease is 5 to 24 fold higher in individuals with HIV than in the general population (primarily due to C, W, and Y), and evidence that MCV4 is immunogenic and safe in children, although having a lower seroresponse in adolescents and rapid immunogenic waning in adolescents and young adults, the ACIP voted to add HIV infection to the list of high risk conditions recommended to receive MCV4 in persons ages > 2 months of age.
Persons who have not previously been vaccinated should receive a two dose primary series (0, 2 months), and since HIV is a life-long condition, persons with HIV should continue to receive boosters at the appropriate interval: after 3 years if age <7 years at previous dose and every 5 years if age > 7 years at previous dose.
Vaxchora® (CVD 103-HgR) live-attenuated cholera vaccine was approved for use in adult travelers to areas of active cholera transmission. It is administered orally in one dose. The optimal timing of the vaccine is 10 days prior to travel, and there is no upper time limit. The ACIP recommendation will contain information concerning the added risk for poor clinical outcome when cholera is contracted in people with blood type O or with low gastric acidity (such as those on protein pump inhibitors).
The previous formulation of this vaccine had evidence that it could be co-administered with oral typhoid vaccine, and its efficacy may have been reduced with the use of oral antimalarial chloroquine. The new formulation has not been tested for co-administration. There is no recommendation for re-immunization at this time.
Evidence was presented in the ACIP meeting to inform the committee concerning future vaccine recommendations.
A biologics license application (BLA) has been submitted to the FDA requesting approval for FLULAVAL® quadrivalent for administration to infants and toddlers age 6 through 35 months. Of note is the dose of this product. While Fluzone is provided at 0.25mL dosing for age 6 through 35 months, FLULAVAL was studied at twice that dose and antigen content, (0.5 mL and 15 micrograms per strain). Immunogenicity is non-inferior with GMT and seroconversion rates all favoring the higher dose FLULAVAL. Superiority was noted in the influenza B strains when comparing FLULAVAL to Fluzone. FLULAVAL would be available in pre-filled syringes or multi-dose vials.
Human Papilloma Virus (HPV) vaccine
Europe has approved a 2-dose HPV vaccine schedule, and the World Health Organization (WHO) changed their recommendation in 2014 from a 3-dose schedule to a 2-dose schedule for those starting the series before age 15 years. No loss of seroconversion is seen in trials with 2 doses rather than 3 doses, and Geometric Mean Titers (GMTs) in in a 2-dose schedule for girls and for boys age 9 to 14 years was non-inferior to a 3-dose series in young women age 16 to 26 years.
The ACIP supports moving ahead with a 2-dose series with dose 2 given 6 to 12 months after dose 1. A 3-dose series would still be recommended for those who start their series after 15 years of age and for persons of all ages who are immunocompromised or have HIV. This recommendation will be voted on in the October meeting.
Meningococcal B vaccine, Trumenba® has been approved by the FDA for a 2-dose series in a 0, 6 month dosing schedule. GMTs are lower in the 2-dose schedule and there are still questions about the duration of protection provided by a 2-dose schedule. The ACIP is planning to review a possible recommendation with guidance about the appropriate situations to use either a 2-dose or a 3-dose schedule for Trumenba® in their October meeting.
The timing of the second dose in the 3-dose series has also been modified by the FDA to allow for an interval of 1-2 months after the first dose rather than an interval of 2 months.
If you have any questions regarding immunization, feel free to contact Tamara Sheffield, MD, MPA, MPH, Medical Director, Community Health and Prevention, Intermountain Healthcare, at (801) 442-3946, or Tamara.Shefflied@imail.org.