H1N1 Vaccines Safe, Immunogenic in Single Dose

H1N1 Vaccines Safe, Immunogenic in Single Dose

By Michael Smith, North American Correspondent, MedPage Today
Published: September 10, 2009
Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston and
Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner
Two investigational vaccines against the pandemic H1N1 flu appear to be safe and to yield a robust immune response with a single dose.

Those findings -- contained in two preliminary reports published online today in the New England Journal of Medicine -- are reassuring, experts said.

Among other things, vaccines that can produce an immune response with a single dose will stretch what is predicted to be a short supply of the drugs, according to Kathleen Neuzil, MD, of the University of Washington in Seattle.

Also, she wrote in an editorial accompanying the papers, immunity will appear more quickly -- soon after vaccination rather than after two doses at least three weeks apart.
Action Points

* Explain to interested patients that a vaccine against the pandemic H1N1 flu is thought to be the best protection, but there had been worries that any vaccine would need at least two doses.

* Note that two preliminary reports suggest a single dose is all that will be needed.

The reports are "welcome and reassuring," Neuzil said, especially since a third online paper reported that few people currently have any immunity to the new H1N1 strain.

In that study, Jacqueline Katz, PhD, and colleagues at the CDC tested stored serum samples of people vaccinated against seasonal flu or the 1976 swine flu strain.

Vaccination against seasonal flu produced little protection against the H1N1 pandemic strain in any age group, Katz and colleagues found. But vaccination against the 1976 swine flu among older people did substantially boost immunity against the new pandemic virus. Some individuals born before 1950 also appeared to have antibody to the new H1N1 strain without having received the 1976 swine flu vaccine.

The first of the preliminary reports published today is from a continuing study in Australia, where researchers are testing an inactivated H1N1 vaccine in a cohort of 240 volunteers, randomized to get either 15 or 30 micrograms of the drug.

Three weeks after vaccination more than 90% of volunteers had a robust immune response, according to Michael Greenberg, MD, of CSL, the vaccine's manufacturer.

Specifically, antibody titers of 1:40 or more -- a level associated with immune protection -- were observed in 116 of the 120 volunteers (or 96.7%) who got the lower dose.

The same level was seen in 112 of 120 participants (or 93.3%) who got the higher dose.

The researchers said they saw "no deaths, serious adverse events, or adverse events of special interest." Local discomfort at the injection site was reported by 46.3% of participants and systemic symptoms such as headaches by 45%.

The second study, led by Iain Stephenson, MD, of Leicester Royal Infirmary, in Leicester, England, tested an H1N1 vaccine with and without an oil-in-water adjuvant, known as MF29.

Volunteers -- 175 adults, ages 18 to 50 -- were randomly assigned to receive:

* Two intramuscular injections of adjuvanted vaccine containing 7.5 micrograms of hemagglutinin on day zero in each arm
* Or one injection on day zero and the other on either day seven, 14, or 21
* Or two 3.75-microgram doses of adjuvanted vaccine 21 days apart
* Or 7.5 micrograms or 15 micrograms of non-adjuvanted vaccine, again given 21 days apart

The researchers are reporting data from 100 volunteers -- those who got the 7.5-microgram dose of the adjuvanted vaccine. (The manufacturer earlier gave some details of the findings. See Novartis Says Swine Flu Vaccine Works Quickly)

In that cohort, Stephenson and colleagues found, 86% of the volunteers reported adverse reactions after one or both doses -- primarily injection site pain and muscle aches. The reactions were generally mild or moderate and resolved after 72 hours, the researchers said.

For those who got two doses, the researchers said, more than 90% achieved "seroprotection" by day 21 -- defined as an antibody titer of 1:40 or more -- regardless of the dosing schedule.

One group included in the analysis had been given the first dose but had not yet had the second shot. In that group, 80% had seroprotection by day 21.

"Generally, I think the results are good news," said John Treanor, MD, a vaccine expert at the University of Rochester in Rochester, N.Y.

He noted that the vaccine recently approved in China reportedly had good results with a single dose and other studies are still under way that should have data available soon.

"The overall impression I think, is that for adults, a single dose of vaccine will be sufficient," Treanor said.

One thing to consider, he said, is that the Australian study took place during the epidemic in that country, so that prevaccination antibody levels were higher than expected.

But the level of protection the researchers found is high enough that it seems likely the conclusion will stand up, he added.

The vaccines thus far have been given to healthy adults, so immunization of other groups may produce different antibody responses.

Richard E. Besser, MD, a former CDC deputy director who is now senior health and medical editor at ABC News, was also enthusiastic -- especially about the possibility that a single dose could produce immunity.

"This is very exciting news. It has many implications. It could double the number of adults who could be vaccinated. It will greatly simplify vaccination programs by no longer needing to track people between the first and second dose. It will greatly reduce the costs of vaccination programs," Besser said.

The results of the British study are also encouraging, Treanor said, although it's still too early to say what role the oil-in-water adjuvant is playing.

John Bartlett, MD, of Johns Hopkins Medical Institution, in Baltimore, agrees that the findings are encouraging. "The good news is that it suggests a single dose may be adequate," he said.

That's important for logistical reasons, as well as to stretch an available vaccine as far as it will go, said Robert Field, JD, PhD, of Drexel University in Philadelphia.

"It is dramatically easier to administer one shot than two," he said. "With a two-dose regimen, many people will neglect to get the second shot" -- sometimes for the simple reason that they don't know where to get the second shot.

"For instance," Field said, "if someone gets the first one at a supermarket, do they have to return there, can they get it at another supermarket, can they go to their physician's office, or can they go elsewhere?"

The Australian study was supported by CSL and the Department of Health and Aging of the Australian government. All authors report being employees of CSL and several report having an equity interest in the company.

The British study was supported by University Hospitals Leicester and Novartis. Stephenson reported financial links with Novartis Vaccines, Sanofi Pasteur, Baxter Vaccines, Hoffmann–La Roche, and GlaxoSmithKline.

The CDC study was supported by the CDC. Katz reported research support from GlaxoSmithKline.

The editorial author reported no conflicts.

This article was developed in collaboration with ABC News.

Primary source: New England Journal of Medicine
Source reference:
Greenberg MA, et al "Response after one dose of a monovalent 2009 influenza A (H1N1) vaccine -- Preliminary report" N Engl J Med 2009; DOI: 10.1056/NEJMoa0907413.

Additional source: New England Journal of Medicine
Source reference:
Clark TW, et al "Trial of influenza A (H1N1) 2009 monovalent MF59-adjuvanted vaccine -- Preliminary report" N Engl J Med 2009; DOI: 10.1056/NEJMoa0907650.

Additional source: New England Journal of Medicine
Source reference:
Hancock K, et al "Cross-reactive antibody responses to the 2009 pandemic H1N1 influenza virus" N Engl J Med 2009; DOI: 10.1056/NEJMoa0906453.

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