health.mil

Matt Pueschel  |  FHP&R

May 10, 2011

New military recruits will soon be able to rest a little easier during basic training.

In partnership with the pharmaceutical industry, the U.S. Department of Defense (DoD) Military Health System has developed a new vaccine to prevent febrile respiratory illness caused by adenovirus types 4 and 7 that often occurs among military recruits during basic training. Adenovirus can cause severe flu-like illness and is commonly transmitted person-to-person in basic training sites where recruits live in close quarters. 

The Food and Drug Administration (FDA) Center for Biologics Evaluation and Research (CBER) approved the Adenovirus Type 4 and Type 7 Live Oral Vaccine on March 16. It is indicated for active immunization to prevent febrile acute respiratory disease caused by Adenovirus Types 4 and 7, and is approved solely for use in military populations 17- through 50-years of age. The current DoD policy is to administer the vaccine only to new military recruits.


U.S. Navy midshipmen stand in formation during career orientation training for midshipmen (CORTRAMID) at Camp Geiger, N.C. (U.S. Marine Corps photo by Lance Cpl. Felicia M. Couture/Released)The DoD will be the only user of the vaccine, which is primarily aimed at ensuring the health and safety of new Service members. “It makes for a smoother basic training program. These adenovirus illnesses are preventable,” said John Lucas, ScD, Deputy Director of the Medical Countermeasures (MCM) Directorate in the Office of Force Health Protection and Readiness who also serves as DoD’s Health Affairs representative on the Integrated Product Team for the vaccine.

The vaccine was developed specifically for the U.S. military by Teva Pharmaceuticals USA, Inc./Barr Laboratories, Inc., under a DoD contract managed by the U.S. Army Medical Materiel Development Activity in the Army’s Medical Research and Materiel Command. DoD will administer it to recruits during in-processing at basic training locations later this calendar year. Vaccinations at recruitment sites may begin within as early as three months from the date of the FDA licensure. “The plan is to get the vaccines to people starting this year,” said Dr. Lucas.

Since 2001 the Defense Health Program has spent about $107 million to develop the vaccine, and additionally will spend more than $45 million annually on contracting for the next several years to produce and administer it. Under the FDA license, Teva Pharmaceuticals USA, Inc./Barr Laboratories, Inc., is approved to manufacture, fill, label, and package the final formulated product.

A single vaccine dose consists of two tablets taken orally, one tablet each for adenovirus types 4 and 7. Each tablet should be swallowed whole, without chewing, to avoid releasing the virus in the upper respiratory tract, before it gets to the intestinal tract where adenovirus replicates and induces immunity. The Military Vaccine (MILVAX) Agency, which oversees training and education for administration of the vaccine, is providing education to recruitment sites on how to efficiently administer the two tablets to as many as 800 recruits a day.

The new vaccine contains live adenoviruses that are shed in the stool for up to 28 days, creating the risk of potential transmission of the virus to non-vaccinated individuals during that period. Prior to vaccination, individuals will receive education and training on sanitation and hygiene measures to minimize this potential transmission risk. “We are developing education/training materials for the recruit sites from two perspectives: 1) an occupational health perspective, which will address the issues surrounding the storage and handling of the vaccine and the disposal of the containers, and 2) a vaccine administration perspective, which will address how to screen for contraindications and how to administer the vaccine to each recruit,” said Hayley Hughes, DrPH, CSP, Division Chief of Safety and Evaluation for MILVAX.

Dr. Lucas said recruits should be careful and use proper hygiene and sanitation techniques such as thorough hand washing after receiving the vaccine during the shedding period. “The vaccine provides immunity by increasing your antibodies and protects you against disease,” he advised.

The new vaccine is contraindicated in pregnant women, who will be exempted from receiving it. As part of their post-licensure requirements, Teva Pharmaceuticals USA, Inc., is responsible for administering an adenovirus vaccine pregnancy registry to enroll women who are inadvertently vaccinated while pregnant or become pregnant within six weeks of being vaccinated. The registry’s administrators will monitor their health, their child’s health through the first year of life to detect potential safety signals, and any follow-up care they may receive. The FDA requires the manufacturer to submit a Pregnancy Registry Status Report to CBER annually.

Vaccine administration should further be postponed in recruits who experience a severe allergic reaction, vomiting or diarrhea, or among those who are unable to swallow a whole tablet. The safety and effectiveness of the vaccine has also not been evaluated in immunocompromised individuals.

Teva Pharmaceuticals USA, Inc., is responsible for monitoring uncommon medical events occurring within 42 days of vaccination in the first 100,000 military recruits during the first year of vaccine administration, and conducting a surveillance study for febrile respiratory illness due to vaccine viral shedding using monthly data from the Naval Health Research Center. The company is further required to submit adverse event reports to the national Vaccine Adverse Event Reporting System (VAERS), which is co-managed by FDA and the Centers for Disease Control and Prevention. Anyone can file a VAERS report, including health care providers, manufacturers, and vaccine recipients.

Adenovirus Incidence and Vaccine Efficacy

Adenovirus serotypes 4 and 7 are important causes of febrile acute respiratory disease (ARD) in U.S. military recruits, and can cause acute infections of the respiratory tract, gastrointestinal system, eyes and central nervous system. With the physical intensity of basic training, recruits’ resistance to the adenovirus lowers. Over the past 10 years the virus has affected about 15,000 basic trainees annually, with 3-4 days of illness per event and 1-2 deaths occurring per year due to the virus. “There are a lot of intense physical activities in basic training such as long hikes. Viral resistance can decrease and recruits can become more vulnerable to illness,” Dr. Lucas said.

MILVAX officials said the virus is spread person-to-person mostly in droplet form or through respiratory secretions similar to influenza. Adenovirus-associated illnesses can cause a loss of training time over several days when recruits become ill and may have to be pulled out of the basic training cycle to recover for the next one. “It’s easier to prevent illness from adenovirus from occurring instead of waiting until someone gets ill and potentially has to leave training until the next cycle begins,” Dr. Lucas said, adding that at $111 a dose the vaccine is also cost-effective.


In partnership with the pharmaceutical industry, the U.S. Department of Defense (DoD) Military Health System has developed a new vaccine to prevent febrile respiratory illness caused by adenovirus types 4 and 7 that often occurs among military recruits during basic training. (U.S. Air Force photo by Staff Sgt. Marc I. Lane/Released) According to the Febrile Respiratory Illness (FRI) Surveillance program administered by the Naval Health Research Center at eight basic training sites, adenovirus type 4 remains the predominant cause of FRI among recruits at most training centers. Adenovirus type 14 has also been found at two of these sites.

Approximately 90 percent of recruits are susceptible to adenovirus types 4 and 7 and about one case is found among every 200 trainees each week of basic training (0.5-0.79/100 trainees weekly). Because adenovirus types 4 and 7 can present a serious health threat to Service members during basic training, a year-round vaccination policy will be required among all new recruits due to the absence of any consistent seasonal patterns of infections. “This will be a mandatory vaccine for new recruits,” Dr. Lucas advised.

DoD previously had an adenovirus vaccine through another manufacturer that lowered infections among recruits down to nearly zero in the mid-‘90s, but it was decided to discontinue making it and supplies ran out in the late ‘90s. After illnesses started to reappear, DoD decided to acquire an updated version of the vaccine that met new FDA requirements and manufacturing technology standards. The original vaccine technology was transferred to the new manufacturer, new lab facilities were built to current standards and the vaccine was further developed to meet FDA approval. “The new vaccine is more advanced, has a highly controlled manufacturing technology and the proof (of efficacy) is tighter and protects against disease,” Dr. Lucas said. “It has been proven safe. The vaccine gives a four-fold increase in antibody response to the virus in the bloodstream in 94 percent of people who have been inoculated.”

In the intervening years, DoD has made strides to enhance preventive measures at basic training sites that have reduced the incidence of the virus, such as handwashing, hand sanitizing, the use of surgical masks, rearranging group living spaces, placing beds so that new recruits sleep head to toe, and improving ventilation, air dilution, sterilization and dust suppression.

In the fall of 2004, researchers from the Walter Reed Army Institute of Research conducted a phase 1 randomized, double-blind, placebo-controlled trial of the new live, oral adenovirus types 4 and 7 vaccines to assess their safety and immunogenicity. The results were published in the June 2, 2008 issue of Vaccine and showed that the new vaccine was safe and induced a good immune response in study participants. The most commonly reported adverse events (AE) were nasal congestion (33 percent), cough (33 percent), sore throat (27 percent), headache (20 percent), abdominal pain (17 percent), arthralgia (13 percent), nausea (13 percent) and diarrhea (13 percent), but rates of AE did not differ significantly from those of the placebo group.

Subsequent large-scale studies of the new vaccines in U.S. military recruits showed high efficacy rates in preventing wild adenovirus type 4-associated febrile acute respiratory disease (99.3 percent efficacy) and inducing neutralizing antibody to adenovirus type 7 (about a 94 percent seroconversion rate).

MILVAX officials said they do not anticipate any significant adverse events to occur with the new vaccine, adding that any cases with a possible adverse event would be treated symptomatically through standard supportive care by DoD healthcare providers.

For more information on DoD’s immunization programs and policies, please visit MILVAX’s Web site at www.vaccines.mil or the Medical Countermeasures Directorate at www.fhpr.osd.mil/MedicalCountermeasures. For more news visit www.fhpr.osd.mil.

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