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Update on Influenza A (H1N1) 2009 Monovalent Vaccines

On September 15, 2009, four influenza vaccine manufacturers received approval from the Food and Drug Administration for use of influenza A (H1N1) 2009 monovalent influenza vaccines in the prevention of influenza caused by the 2009 pandemic influenza A (H1N1) virus.* Both live, attenuated and inactivated influenza A (H1N1) 2009 monovalent vaccine formulations are available; each contains the strain A/California/7/2009(H1N1)pdm. None of the approved influenza A 2009 (H1N1) monovalent vaccines or seasonal influenza vaccines contains adjuvants (1--5). CDC's Advisory Committee on Immunization Practices has made recommendations previously for which persons should be the initial targets for immunization with influenza A (H1N1) 2009 monovalent vaccines and has issued guidelines on decisions for expansion of vaccination efforts to other population groups (6). Children aged 6 months--9 years receiving influenza A (H1N1) 2009 monovalent vaccines should receive 2 doses, with doses separated by approximately 4 weeks; persons aged ≥10 years should receive 1 dose (1--4).

The approved age groups for use of inactivated influenza A (H1N1) monovalent influenza vaccines differ by manufacturer (Table). Three manufacturers that produce inactivated vaccines approved for prevention of seasonal influenza (6) also produce formulations of influenza A (H1N1) 2009 monovalent influenza vaccines. Vaccine produced by CSL Limited is approved for use in persons aged ≥18 years (1), vaccine produced by Novartis Vaccines and Diagnostics Limited is approved for persons aged ≥4 years (2), and vaccine produced by Sanofi Pasteur, Inc. is approved for persons aged ≥6 months (3). A live attenuated influenza vaccine (LAIV) manufactured by MedImmune LLC is approved for persons aged 2--49 years (1). The 2009 (H1N1) monovalent LAIV has the same age range for use as the seasonal LAIV and should not be used to vaccinate children aged <2 years, adults aged >49 years, pregnant women, persons with underlying medical conditions that confer a higher risk for influenza complications, or children aged <5 years old with one or more episodes of wheezing in the past year (5).

Influenza A (H1N1) 2009 monovalent vaccine approvals were made on the basis of standards developed for vaccine strain changes for seasonal influenza vaccines, adherence to manufacturing processes, product quality testing, and lot release procedures developed for seasonal vaccines. The age groups, precautions, and contraindications approved for the influenza A (H1N1) 2009 monovalent vaccine are identical to those approved for seasonal vaccines. All influenza vaccines available in the United States for the 2009--10 influenza season are produced using embryonated hen's eggs and contain residual egg protein.

Preliminary data indicate that the immunogenicity and safety of these vaccines are similar to those of seasonal influenza vaccines. An immunogenicity study of an inactivated influenza A (H1N1) monovalent vaccine manufactured by CSL Limited (Parkville, Victoria, Australia) demonstrated that by day 21 after vaccination, antibody titers of 1:40 or more (hemagglutination-inhibition assay) were observed in 116 (97%) of 120 adults who received the 15 μg dose. Local discomfort (e.g., injection site tenderness or pain) was reported by 46% of subjects, and one or more systemic symptoms (e.g., headache, malaise, or myalgia) by 45% of subjects (7). This safety profile is consistent with results from studies of the seasonal influenza vaccine manufactured by CSL Limited (8). In studies of other seasonal inactivated influenza vaccines, rates of adverse events were not significantly different from placebo injections except for arm soreness and redness at the injection site (9). The National Institute of Allergy and Infectious Diseases (NIAID) reported preliminary results of a study among children aged 6 months--18 years. Among children aged 6--35 months, 3--9 years, and 10--17 years immunized with a 15 μg inactivated influenza A 2009 (H1N1) monovalent vaccine (Sanofi Pasteur, Inc., Swiftwater, PA), 25%, 36% and 76%, respectively, developed antibody titers of 1:40 or more (hemagglutination-inhibition assay) after a single dose of vaccine.† Immunogenicity and safety study results similar to those observed for seasonal vaccines also have been reported by the other manufacturers (MedImmune LLC, Gaithersburg, MD and Novartis Vaccines and Diagnostics, Limited, Liverpool, UK, unpublished data, 2009).

Influenza activity attributed to 2009 H1N1 viruses has increased during September 2009 and is expected to continue through the fall and winter influenza season. Surveillance data indicate that the 2009 H1N1 viruses have not undergone substantial antigenic change since they were first characterized in April 2009 and should be well-matched to the monovalent vaccine strain (10). Influenza A (H1N1) 2009 monovalent vaccines will be available in many areas by mid-October. Vaccines against seasonal influenza are available now, and immunization programs and providers should begin or continue administering seasonal influenza vaccines as recommended (5,6). Additional data from clinical trials will be available over the coming weeks, and immunization providers should periodically look for updates on use of influenza A (2009) H1N1 monovalent vaccines at http://www.cdc.gov/flu.

References

CSL Biotherapies, Inc. Influenza A (H1N1) 2009 monovalent vaccine [Package insert]. King of Prussia, PA: CSL Biotherapies Inc.; 2009. Available at http://www.fda.gov/downloads/biologicsbloodvaccines/vaccines/approvedproducts/ucm182401.pdf. Accessed October 7, 2009.
Novartis Vaccines and Diagnostics, Ltd. Influenza A (H1N1) 2009 monovalent vaccine [Package insert]. Cambridge, MA: Novartis Vaccines and Diagnostics, Ltd.; 2009. Available at http://www.fda.gov/downloads/biologicsbloodvaccines/vaccines/approvedproducts/ucm182242.pdf. Accessed October 7, 2009.
Sanofi Pasteur, Inc. Influenza A (H1N1) 2009 monovalent vaccine [Package insert]. Swiftwater, PA: Sanofi Pasteur Inc.; 2009. Available at http://www.fda.gov/downloads/biologicsbloodvaccines/vaccines/approvedproducts/ucm182404.pdf. Accessed October 7, 2009.
MedImmune, LLC. Influenza A (H1N1) 2009 monovalent vaccine live, intranasal [Package insert]. Gaithersburg, MD: MedImmune, LLC.; 2009. Available at http://www.fda.gov/downloads/biologicsbloodvaccines/vaccines/approvedproducts/ucm182406.pdf. Accessed October 7, 2009.
CDC. Prevention and control of seasonal influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2009. MMWR 2009;58(No. RR-8).
CDC. Use of influenza A (H1N1) 2009 monovalent vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2009. MMWR 2009;58(No. RR-10).
Greenberg ME, Lai MH, Hartel GF, et al. Response after one dose of a monovalent influenza A (H1N1) 2009 vaccine---preliminary report. N Engl J Med 2009 [E-pub]. Available at http://content.nejm.org/cgi/reprint/NEJMoa0907413.pdf?resourcetype=HWCIT. Accessed October 7, 2009.
Talbot HK, Keitel W, Cate TR, et al. Immunogenicity, safety and consistency of new trivalent inactivated influenza vaccine. Vaccine 2008;26:4057--61.
Nichol KL, Margolis KL, Lind A, et al. Side effects associated with influenza vaccination in healthy working adults: a randomized, placebo-controlled trial. Arch Intern Med 1996;156:1546--50.
CDC. Update: influenza activity---United States, April--August 2009. MMWR 2009;58:1009--12.

* Food and Drug Administration. FDA approves vaccines for 2009 H1N1 influenza virus. Available at http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm182399.htm.

† National Institutes of Health. Early results: in children, 2009 H1N1 influenza vaccine works like seasonal flu vaccine. Available at http://www.nih.gov/news/health/sep2009/niaid-21.htm.

TABLE. Influenza A (H1N1) 2009 monovalent vaccines approved for use in the United States, October 6, 2009
Vaccine type	Manufacturer	Presentation	Mercury content (μg Hg/0.5 mL dose)	Age group	No. of doses	Route
Inactivated*	Sanofi Pasteur	0.25 mL prefilled syringe	0	6--35 mos	2†	Intramuscular§
		0.5 mL prefilled syringe	0	≥36 mos	1 or 2†	Intramuscular
		5.0 mL multidose vial	25.0	≥6 mos	1 or 2†	Intramuscular
Inactivated*	Novartis Vaccines and Diagnostics Limited	5.0 mL multidose vial	25.0	≥4 yrs	1 or 2†	Intramuscular
Inactivated*	Novartis Vaccines and Diagnostics Limited	0.5 mL pre-filled syringe	<1.0	≥4 yrs	1 or 2†	Intramuscular
Inactivated*	CSL Limited	0.5 mL prefilled syringe	0	≥18 yrs	1	Intramuscular
Inactivated*	CSL Limited	5.0 mL multidose vial	24.5	≥18 yrs	1	Intramuscular
LAIV¶	MedImmune LLC	0.2--mL sprayer**	0	2--49 yrs	1 or 2††	Intranasal
* A 0.5-mL dose contains 15 μg hemagglutinin of A/California/7/2009 (H1N1)pdm. † Two doses administered approximately 4 weeks apart (≥21 days acceptable) are recommended for children aged 6 months--9 years. § The preferred site for infants and young children is the anterolateral aspect of the thigh. ¶ Live attenuated influenza vaccine. A 0.2-mL dose contains 106.5--7.5 fluorescent focal units of live attenuated influenza virus reassortants of A/California/7/2009 (H1N1)pdm. ** Influenza A (H1N1) 2009 LAIV is shipped refrigerated and stored in the refrigerator at 36°F--46°F (2°C--8°C) after arrival in the immunization clinic. The dose is 0.2 mL divided equally between each nostril. LAIV should not be administered to persons with asthma. Health-care providers should consult the medical record, when available, to identify children aged 2--4 years with asthma or recurrent wheezing that might indicate asthma. In addition, to identify children who might be at greater risk for asthma and possibly at increased risk for wheezing after receiving LAIV, parents or caregivers of children aged 2--4 years should be asked: "In the past 12 months, has a health-care provider ever told you that your child had wheezing or asthma?" Children whose parents or caregivers answer "yes" to this question and children who have asthma or who had a wheezing episode noted in the medical record during the preceding 12 months should not receive LAIV. †† Two doses administered approximately 4 weeks apart are recommended for children aged 2--9 years.

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Date last reviewed: 10/8/2009