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Despite controversial year, vaccine development, updates continue in US

BOSTON — Each year there are updates to available vaccines, and 2014 was no exception. In a year which saw the re-emergence of some vaccine preventable diseases, the global spread of diseases such as Ebola and dengue, and a national debate regarding the value of vaccination, the role of vaccine development and improvement is more important than ever.

“Vaccines are one thing we do as physicians that are really important to society and important to the world in general,” said Michael J. Donnelly, MD FACP, FAAP, of the Department of Pediatrics at Georgetown University Medical Center.

In his talk at the ACP Internal Medicine Meeting, Donnelly reviewed the latest in vaccine innovations, updates to current vaccines, and the progress of vaccine coverage toward eradicating some of the world’s most devastating diseases.

Vaccine promotion, uptake

Donnelly began by evaluating the progress of the medical and scientific communities in promoting vaccine uptake and developing quality vaccines. He enumerated a “wish list” regarding what an ideal vaccine should deliver.

“What do we want from our vaccines? We want safety, immunogenicity, and we need them to be efficacious,” he said. “And for the busy practitioner, we need them to be easy. We need to be able to store them, administer them, and get paid for them, so there’s not a barrier to us giving them. More and more, there is a barrier.”

He discussed the U.S. percentages of vaccine coverage for various diseases, citing a flu vaccination rate of just over 40% for adults.

“From there we go down,” he said. “We don’t hit over 60% for anything. So overall, the vaccine rates in the U.S. fall short of where we want them to be.”

Meningococcal disease

The 2014 death of a Drexel University student from serotype B meningococcal disease brought the growing problem of this disease to the forefront. Between 2009 and 2014, there have been five outbreaks at major universities, and Donnelly said there was a fourfold increased risk among university students during the outbreak period. The serotypes of this disease, which is common in infants, children and adolescents, have shifted within these patient populations, he said.

“If you look at infants, you see that most — two-thirds — have serotype B,” he said. “With older adolescents, it used to be mostly C, Y and W135, all of which are contained in the quadrivalent vaccine; now, only 40% are C and Y, and 40% are serotype B. This is obviously important, because meningococcus has such a high case fatality rate.”

A vaccine against meningococcal disease has existed since 1982. Donnelly said it is a polysaccharide vaccine containing serotypes A, C, Y and W135.

“It is about 85% protective,” he said. “The downside is that the immunity wanes over time and doesn’t induce a T-cell response, so in high-risk patients, we usually revaccinate every 5 years, especially in children under age four.”

In 2005, two conjugate vaccines, Menactra (Sanofi Pasteur) and Menveo (Novartis) were developed.

“Conjugate vaccines are important because they contain the same antigen, but they conjugate it to diphtheria toxoid,” Donnelly said. “Conjugate vaccines are much better, especially for polysaccharide antigens, at basically inducing T-cell immunity.  This helps with memory, so you have better immune response down the line, and it also helps with herd immunity.”

Donnelly said the rates of meningococcal disease are highest in newborns up to 1 year of age, and then in adolescents between 16 and 20 years. He said the ACIP recommends vaccination against meningococcal disease between the ages of 11 and 12 years, with a booster at age 16 years.

“Freshmen living in dormitories are at higher risk than anyone,” Donnelly said. “That is why these ACIP recommendations came to be. When we started giving the vaccine at [age] 11 [years], we realized the antibodies went down over time.”

Other patients at high risk are those with complement deficiency, patients with functional or anatomic asplenia, immunologists traveling to sub-Saharan Africa, and U.S. military recruits.

Pregnant women can be vaccinated against meningococcal disease, but they should receive the polysaccharide vaccine, since more data exist on that vaccine in this patient population, he said.

Donnelly said clinicians should be aware of the patients in their practice for whom meningococcal disease vaccine would be indicated.

“Right now there are no general recommendations on how to give these vaccines,” he said. “Remember, though, that young adults may not have had boosters at age 16, so for new folks coming into your office, remember to ask them about meningococcal vaccines.”

Herpes zoster updates

Donnelly also provided an update on a new adjuvant herpes zoster subunit vaccine. He said the current vaccine is the same one that has been in use since the 1960s.

“What we use in the U.S. is the same chickenpox virus we give to kids, but increased from 1,350 platform units to probably 18,000 platform units,” he said. “It’s just a ramped-up version of the vaccine we give to kids, licensed to folks [aged] 60 [years] and older.”

Donnelly said the vaccine is given to older patients due to the prevalence and duration of post-herpetic neuralgia in this population.

“Post-herpetic neuralgia is obviously a problem,” he said. “Older folks, over age 60, are more likely to continue to have pain at year 3.”

Vaccinating older adults against herpes zoster has been effective in decreasing the disease, as well as the pain associated with it. 

“We saw a 50% decrease in herpes zoster in all age groups, and a two-third reduction in post-herpetic neuralgia,” he said.

However, the duration of protection conferred by the vaccine appears to be limited, with a roughly 30% reduction in protection at 10 years.

“This is a big problem, this decreased efficacy over time,” he said.

The new vaccine, HZ/su (GlaxoSmithKline), which uses varicella zoster glycoprotein E, recently finished phase 3 trials in the U.S.

“They did a study in Europe, 3 years follow-up in about 16,000 participants, and it worked tremendously well across all age groups,” Donnelly said. “It had a 97% efficacy rate, and that was fantastic. The question will be what happens in the next several years for licensing rights in the U.S.”

The study did show a high rate of local reactions, with 17% of study participants experiencing a grade-3 reaction. Moreover, the duration of protection has not yet been demonstrated.

“We’ll see, down the road, how long it lasts,” he said.

In terms of co-administration of the zoster vaccine with PPSV23, different health care agencies are not entirely in accord on their recommendations.

“One study showed geometric mean titers were different if you gave them at the same time vs. one month apart, so the FDA recommends they be given 4 weeks apart,” Donnelly said.

The zoster vaccine should be considered in younger patients who are sensitive to neuralgia due to conditions such as chronic pain or depression, he added.

“The CDC says if someone will tolerate zoster or neuralgia very poorly, then perhaps that’s a reason to give the vaccine early,” Donnelly said.

In the pipeline
Donnelly reviewed the strains that were chosen by the FDA to go into next year’s vaccines.
“The beauty of the crystal ball is that the WHO, and then the FDA, decide this in February for the next year, because the lead time of growing things from eggs takes so long,” he said. “We’re going to the H1N1 pandemic 09 type virus, so that and the H3N2 again this year.”

In the pipeline, there is a potential pediatric dengue vaccine being developed. Donnelly said studies recently conducted on this vaccine demonstrated some degree of protection in children from Central and South America.

An enterovirus 71 vaccine is also in development, as well as a virus-like particles (VLP) vaccine against norovirus.

Donnelly discussed a potential Ebola virus vaccine; Ebola is still a problem in many parts of the world, such as Sierra Leone and Guinea.

Political or personal?
The issue of vaccination came to the public’s attention after a December 2014 outbreak of measles, which had been declared eliminated in the US in 2000. The outbreak may, in part, have been attributed to vaccine-resistant attitudes among parents.

“Most of the 111 cases that occurred in the U.S. were clustered around California, where we see a lot of vaccine resistance,” Donnelly said. “Of the 111 patients, 49 were unvaccinated, 12 were too young, 28 were purposely unvaccinated, and about 6% had a two-dose vaccine.”

This raised the issue of compulsory vaccination and sparked debate among parents, whose stances on the matter will necessarily impact children who play or attend school together.

“The important thing here is that ignorance could fuel a resurgence and a serious spiral back to illness,” Donnelly said.

The opposition to mandatory vaccination may be rooted in suspicion of government or a desire for freedom of choice, and has proponents on both sides of the political aisle, he added.
“The views really are spread throughout the political spectrum,” he said. “It’s less political and more personal.” – by Jennifer Byrne

For More Information:

Donnelly MJ. MTP096. Vaccines for the busy internist: Updates and pearls from the Meds-Peds world. Presented at: ACP Internal Medicine Meeting; April 30-May 2, 2015; Boston.

Disclosure: Donnelly reports no relevant financial disclosures.