WSJ on meningococcal vaccine for adolescents

Today's Wall Street Journal has a story about meningococcal vaccine -- the cause of many cases of bacterial meningitis -- and the obstacles faced by efforts at vaccinating adolescents. The story, "Quelling a Killer: The Case For the Meningococcal Vaccine," uses the stories of a few victims of bacterial meningitis to illustrate the rapid and severe course of the rather rare disease in the U.S. Estimates vary, but the WSJ story says that 1,400 to 2,800 cases occur annually, roughly 10% of which are fatal.

Routine vaccination (with SanofiPasteur's Menactra) is recommended for all 11-12 year olds, many colleges and universities require vaccination for students living in dormitories (a high-risk group), and now states such as New Jersey are adding the vaccine to those required for school entrance. Despite these efforts, vaccination rates among recommended populations have ample room for improvement.

As these types of stories tend to do, the article includes back-to-back quotes from Paul Offit and Barbara Loe Fisher on the merits and possible concerns, respectively, associated with routine vaccination of adolescents.

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Speaking of the Wall Street Journal, a lengthy story appeared in July -- "Get Your Shots: Adults Need Vaccines, Too" -- detailing the growing number of vaccines recommended for another population, adults, for which awareness of vaccination efforts lags in comparison to pediatric vaccination programs.

Caplan on college meningococcus vaccine requirements

Last week, MSNBC.com published a story titled, "Killer at college: Meningitis threatens students; Mandatory vaccine for deadly bacterial disease sparks debate." The story provides a detailed account of the threat posed by bacterial meningitis on college campuses and efforts by many states to require vaccination for college freshmen (or a signed waiver declining the vaccine). More information about meningococcal vaccination is available from this CDC website, and details about SanofiPasteur's Menactra (the vaccine recommended for adolescents) is available here.

In response to this story, Penn's Art Caplan wrote a commentary for MSNBC.com that was posted last Thursday: "Students' meningitis shots should be required." He writes, in part,

"Americans do love choice. But they also hate to lose a child, a sister or a granddaughter. Sometimes choice ought to yield to common sense and evidence. We ought [to] be doing all we can to get young people vaccinated against meningitis and to make sure that the costs of doing so are covered."

The importance of this issue was illustrated by tragic news on our own campus Sunday of the death of a Penn sophomore from bacterial meningitis. Here is coverage from The Daily Pennsylvanian and The Philadelphia Inquirer.

At Penn, all students living in on-campus dormitories are required to be vaccinated with Menactra or sign this waiver citing medical contraindications or religious objections to the vaccine. (This policy is in accordance with a 2002 Pennsylvania law.)

News reports note that the victim lived off-campus during the current school year, but nearly all Penn students live on-campus during their freshman year, making it likely that the vaccination requirement applied to the student one year ago. No information has been made public regarding her vaccination status.

Hitting the bull's eye for pandemic flu vaccine development

In this month's Lancet Infectious Diseases, a commentary by Sambhara, Bridges, and Poland offers an update on progress toward pandemic influenza vaccine development in the wake of the licensure of Sanofi Pasteur's pre-pandemic vaccine this spring.

The title of the short commentary sums up the authors' assessment: "H5N1 vaccine hits the target, but not the bull's eye." (free abstract). Complementing this metaphor is a graphic which illustrates the specific areas that need to be addressed to produce the "ideal pre-pandemic vaccine." Such a vaccine would be safe (of course), require a single dose with a small amount of antigen, provide long-lasting immunity, and be stable (i.e., capable of remaining potent even if stored for some time).

Given that the Sanofi Pasteur vaccine licensed in April falls far short of these goals, the authors advocate directing research efforts toward these aims in particular.

Speaking of pandemic influenza research, WHO posted on their website late last week a series of tables summarizing the impressive number of vaccine candidates for which clinical trials are underway. As the tables show, while H5N1 is properly commanding the overwhelming majority of attention of late, it is not the only influenza strain with pandemic potential that has attracted the interest of researchers.

With respect to pandemic planning in the U.S., another update was issued late last week by HHS secretary Michael Leavitt. Here's the full report as well as coverage from CIDRAP News. In a brief section on vaccines, the report states that the current pre-pandemic stockpile includes sufficient doses for 6 million people, with a 5-year goal of building enough capacity to produce vaccine for all Americans within six months of 'the' pandemic virus' first appearance.

Sanofi flu vaccine plant opens, doubling capacity

The front page of Friday's Philadelphia Inquirer featured a photo of a gloved hand inspecting a tray of eggs. The news? The completion of Sanofi-Pasteur's new flu vaccine plant in Swiftwater, PA.

Some of the numbers in the story: Construction cost $150 million; at full capacity, 600,000 eggs will be used daily, and the plant will double Sanofi's current flu vaccine capacity from 50 to 100 million doses annually.

As the millions of unused doses of seasonal flu vaccine last winter demonstrated, ensuring adequate supply is not a major issue for seasonal flu vaccination efforts. (The far greater challenge is increasing demand among the many populations in which annual vaccination is recommended).

However, Sanofi's new Swiftwater plant could also be used for avian flu vaccine production. (In fact, the Inquirer headline blared, "New Pa. vaccine plant poised for pandemics.") Not only would there be an immediate need for far greater capacity in a pandemic, but the possibility of multiple doses required to provide adequate immune protection could effectively cut avian flu vaccine supply by 1/2 or 1/3, depending on whether 2 or 3 doses are needed.

To that end, Sanofi is in the process of retrofitting an adjacent facility (courtesy of a $77 million federal grant) to increase capacity even further, to 150 million doses, by 2010.

By the way, while the news last week was that construction of the Swiftwater facility was complete, FDA approval is needed before operations can begin. Opening is not expected until late 2008.

Sanofi 5-in-1 pediatric vaccine receives FDA recommendation

News late last week that Pentacel, a 5-in-1 vaccine manufactured by Sanofi Pasteur, received a recommendation from an FDA advisory committee that typically signals imminent licensure in the U.S. Here's the story from Bloomberg.com and the Sanofi press release. According to it, the vaccine could reduce the total number of recommended pediatric vaccine doses by seven.

Pentacel provides protection against diphtheria, pertussis, tetanus, polio, and Haemophilus influenzae type B (Hib). It has been licensed and used in nine countries, including Canada, since its introduction in 1998. If licensed for U.S. use, the vaccine would be the second 5-in-1 vaccine available, joining GSK's Pediarix, which contains four common constituents to Pentacel (Pediarix includes hepatitis B vaccine instead of Hib).

For advocates of vaccination, there is great value in these kinds of combination vaccines, which reduce the number of doses (and office visits) necessary to complete the increasingly longer pediatric vaccination schedule. More visits mean an increased likelihood of missed appointments, missed doses, and incomplete vaccination series. Critics of U.S. vaccination policy, however, express concern about 'overloading' infants' immune systems with multiple vaccines at a single visit, and resulting in a variety of known and unknown adverse effects. At present, there isn't evidence that supports this hypothesis.

Potency concerns for pandemic flu vaccine stockpiles; HHS planning update; more contracts awarded

For months, we've been discussing some of the many challenges and potential problems associated with the "pre-pandemic" avian flu vaccines currently being developed, tested, and stockpiled. More reason for concern came late last week, when this CIDRAP News story reported that a significant percentage of the stockpile has lost potency, resulting in a one-million-person decrease in the number of people who could potentially be protected by vaccine doses currently on hand (3 million, down from 4 million in an HHS document released in July). Here's an excerpt from the story, quoting an HHS spokesman:

"'All vaccines have shelf lives,' Hall told CIDRAP News. 'The early vaccine that was purchased, the first lots, have begun to lose their potency.'

He said the potency has begun to decrease for 'the majority' of doses in the stockpile, adding, 'That doesn't mean it goes from 100 percent to zero percent' or that the doses would be unusable."

On Friday, a day after the story above appeared, the same HHS spokesman seemed to walk back his earlier comments in this CIDRAP follow-up, explaining that only 20% of the current doses on hand are losing potency, not "a majority," as he previously said. Either way, it should come as a surprise to no one that these vaccines have a limited shelf life, an issue avoided by seasonal flu vaccines on account of their annual reformulations. Even with full potency, the vaccine doses in question are from "clade 1" virus samples from 2004. Since early this year, vaccine development has been based on a 2005 sample, working toward "clade 2" vaccines expected to be a closer fit to a possible pandemic strain.

All of this news came as a result of the release last week of the latest HHS Pandemic Planning Update. Not a lot of news in the 13-page report (and, thus, virtually no news coverage about its release), but it provides a good overview of the current status of U.S. planning and spending.

Finally, HHS announced today that another $200 million in contracts have been awarded to Sanofi Pasteur, Novartis, and GlaxoSmithKline for an additional 5.3 million doses of "clade 2" pre-pandemic vaccines, enough to vaccinate roughly 2.7 million people. (Here's the story from Reuters.) This would double the current stockpile (notwithstanding further decreases in potency of older vaccines), but still represent only a bit more than 1/4 of the goal of having enough vaccine stockpiled for 20 million Americans.

From MMWR: childhood & 65+ vaccination rates, 2006-07 adult schedule, and Menactra safety update

A great deal of news on vaccines and vaccination efforts has appeared in recent issues of the CDC's Morbidity and Mortality Weekly Report. Here are some items of note:

• "Childhood Influenza Vaccination Coverage -- United States, 2004-05 Influenza Season" and "Influenza and Pneumococcal Vaccination Coverage Among Persons >65 Years -- United States, 2004-05." With flu cases starting (very slowly) to appear, these two pieces offer some data on the effectiveness of efforts to vaccinate two populations at higher risk of influenza-related complications. For children, the headline is that young children (19-35 months) had a substantially higher vaccination rate in the 04-05 season than for the previous year -- likely attributable to stronger ACIP recommendations. However, the overall percentage of fully vaccinated children in this age group was still very low (17.8%). For 65+ adults, the reverse phenomenon is true: both flu and pneumococcal vaccination rates are over 60%, but flu vaccination rates in 2005 were 4% lower than a year earlier. (The MMWR story notes that all of these numbers are well below the goal of 90% included in Healthy People 2010.)

• Better news can be found in this report, "Vaccination Coverage Among Children Entering School, 2005-2006 School Year." Compiling the latest data available, a editorial note accompanying the report explains, "More than half of reporting states indicate that they have already reached the Healthy People 2010 goal of >95% coverage for each of the vaccines recommended by the Advisory Committee on Immunization Practices (ACIP); the remaining states are making progress toward this goal."

• The 2006-2007 Recommended Adult Immunization Schedule, approved by the ACIP at their June meeting, has been published. Particularly because of efforts made at simplifying the schedule's design, the document is a great source for a general overview of recommended vaccinations in the 18+ population.

• One final item provides an update on reports of cases of Guillain-Barre Syndrome (GBS) among recipients of Menactra, Sanofi Pasteur's meningococcal vaccine. (We've written previously about this story in April.) A total of 17 cases have been reported with a suspected link to Menactra vaccination. As the report explains, analysis of these cases suggests a slightly increased risk of GBS among Menactra recipients, but the risk of meningococcus itself is among the reasons why no change in the current recommendation is being made at this time.
  

FDA approves 2006-2007 flu vaccines

News from Washington yesterday that the FDA approved the vaccines to be used for the upcoming flu season. Here's the FDA press release and AP story regarding the announcement.

These approvals are an annual occurrence, as manufacturers produce flu vaccines including the specific strains of the virus recommended by WHO and FDA. There are four vaccines available:

• Fluvirin (Novartis Vaccines, formerly Chiron)
• Fluarix (GSK)
• Fluzone (Sanofi Pasteur)
• FluMist (Medimmune)

FluMist is the increasingly popular nasally-administered vaccine, the other three are injected (and few patients know which of the three they receive). In total, the FDA estimates a supply of approximately 100 million doses in the U.S. for the season.

Ominous signs for a flu vaccine shortage next winter? Already?

Describing a scene reminiscent of frenzied calling to Ticketmaster for hard-to-get concert tickets, the Allentown Morning Call reports that Sanofi Pasteur confirmed pre-orders for all 50 million doses of its 2006 flu vaccine inventory, selling out in less than 8 hours. Yes, that's for the next flu season, still 9 months away.

The story explains,

"Sanofi, the only maker taking orders directly from doctors, hospitals and other buyers, doubled the phone lines and online ordering capacity, 'but the outpouring far exceeded our expectations,' [a spokesman] said. Normally, the vaccinemaker receives 1,500 calls a day, but on prebooking day, Lavenda said the number of callers trying to get through reached 400,000 and online hits surged 500 percent.

'We can make 50 million doses, maybe a bit more, but the demand far exceeds that. … We feel bad, but we can't stretch our capacity to meet the entire nation's needs.'"

Before we start heralding a repeat of the 2004 supply problems, it's worth noting that (barring another Chiron debacle) the flu vaccine supply outlook is far healthier this time around. Sanofi is one of four currently licensed manufacturers in the U.S., with a fifth likely to join the market by fall.