# 8283
Over the weekend we’ve seen a number of media reports (see Vaccine developed as China reports more H7N9 cases, Vaccine development progresses as China reports more H7N9 cases), that quite frankly, make it sound as if a vaccine is just around the corner. Most of these reports close by saying:
Officials with the Shanghai Public Health Clinical Center said that their genetically engineered vaccine had passed preliminary animal tests on laboratory mice. Once the vaccine passes clinical tests that prove its effectiveness in protecting humans, it will be put into use.
Reassuring, but not terribly specific as to how long clinical trials might take or the possibility that their vaccine might not pass muster. As I’ve mentioned before, attempts at making H7 avian flu vaccines have seen challenges in the past.
Last May we saw an analysis of some of the problems inherent in creating and deploying an H7N9 vaccine published in JAMA, penned by CIDRAP’s Michael T. Osterholm, PhD, MPH; Katie S. Ballering, PhD; and Nicholas S. Kelley, PhD.
Major Challenges in Providing an Effective and Timely Pandemic Vaccine for Influenza A(H7N9)
Michael T. Osterholm, PhD, MPH; Katie S. Ballering, PhD; Nicholas S. Kelley, PhD
JAMA. 2013;():1-2. doi:10.1001/jama.2013.6589.
Published online May 9, 2013
Issues such as the correct amount of antigen per shot, the timing or need for a booster shot, the incidence and severity of side effects, and even the need for an adjuvant are usually sorted out during several rounds of clinical (human) testing, something that can take months or even years.
Work is being done – not only in China - but in Japan, Taiwan, and the United States on developing a suitable H7N9 vaccine.
Last September (see NIH Begins Phase II Clinical Trials On H7N9 Vaccine Candidates) the NIH released a detailed summary of their plans to test a variety of H7N9 vaccine formulations across two clinical trials - involving as many as 1700 volunteers - who will receive various strength H7N9 vaccines (adjuvanted and non-adjuvanted).
When complete, we should have a much better idea of what will be involved in creating a pandemic H7N9 vaccine. Full results, however, are not expected until December of 2014.
Today, via China’s Global Times, we’ve a more complete report on development of their H7N9 vaccines - that a bit confusingly talks about serum antibodies as a `vaccine’ – and paints a less than sanguine picture on when a `vaccine’ might be available.
First the report, then I’ll be back with more.
Clinical trials for H7N9 vaccines
Global Times | 2014-2-10 0:58:01
By Fang YangResearch fellows have made applications for human clinical trials of several new H7N9 vaccines in the wake of increasing reports of cases nationwide, The Beijing News reported on Sunday.
Scientists in Shanghai have developed a genetically engineered vaccine for the H7N9 bird flu virus and have now entered the clinical trial application phase, officials under the Shanghai Public Health Clinical Center announced Friday.
"We injected the H7N9 virus into 30 lab mice after inoculating them with the vaccine, and none of them died after 30 days," Xu Jianqing, a professor with the center, was quoted as saying by the Labor Daily.
The average incubation period for H7N9 is three to four days, according to the Xinhua News Agency.
Xu said the vaccine will be used for high-risk groups in the future, including workers at poultry markets and housewives.
The center also announced that the antibodies against the H7N9 virus, which could lead to a cure for those already infected, will finish invitro tests in a month and go through clinical trials.
However, experts believe that clinical tests are still at an early stage, and it will take years before the vaccine could be used on humans.
It’s not completely clear from this article whether the timeline of `years’ before a vaccine would be available applies to a traditional prophylactic vaccine, the `antibody treatment’ for someone already infected, or both.
Nor is it clear whether `antibodies’ treatment refers to serum antibodies harvested from people who have been infected by H7N9 and recovered (a technique China has tried with varying success against H5N1 & H1N1 ) called Convalescent Plasma or the newer, high-tech field of Human Monoclonal Antibodies (moAb), that are hoped will work against a wide variety of influenza viruses (see Monoclonal Antibodies Revisited).
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Three years ago , in CID Journal: Convalescent Plasma Therapy For Severe H1N1, I described the process:
Blood is collected from people that have been infected and have recovered, and through a process called plasmapheresis, the blood cells are removed leaving only blood plasma.
This is done by passing the blood through a special filter, or by using a centrifuge. The remaining blood plasma will contain antibodies that could then be injected into severely ill patients.
Convalescent plasma could, theoretically, be used as either a treatment for someone already infected, or as a temporary prophylactic, to prevent infection.
There is more to it, of course.
The donor must be checked for a variety of blood borne diseases (i.e. hepatitis B, hepatitis C, Syphilis, and HIV), and then the plasma is usually heated to inactivate other possible pathogens.
A year ago the NIH announced their intention to study this sort of treatment for influenza (see NIAID Announces Three Flu Treatment Clinical Trials), under clinical trial Safety and Efficacy of Investigational Immune Plasma in Treating Influenza A (NCT01052480).
But whether plasma derived or Human Monoclonal Antibodies, both are highly experimental and difficult to produce in large quantities.
While work is being done on an H7N9 vaccine, and there are hopes that a practical one can be created, we are still a long way from having any quantity of commercial vaccine available to the public.
Which means, should the H7N9 virus threaten this spring or even next fall, we will be looking to NPIs (Non Pharmaceutical Interventions like social distancing, school closures, hand hygiene & masks) and neuraminidase (NA) inhibiting antiviral drugs (NAIs) like oseltamivir (Tamiflu ®) and Zanamivir (Relenza ®) to help mitigate its impact.
The creation of a safe, immunogenic H7N9 vaccine is only the first challenge. It must then be mass produced, and then deployed in an orderly and efficient manner.
Difficult decisions will have to be made on vaccine prioritization, and global distribution. And those decisions would not likely be made until a pandemic threat had coalesced.
If, as expected, it will require 2 shots - 4 weeks apart to confer a reasonable level of immunity, the logistics of delivering the vaccine grow even greater.
None of which is to suggest that the pursuit of a vaccine is a futile one. While an H7N9 vaccine would be unlikely to be available during the opening months of a pandemic, it would be extremely useful in limiting the effects of the virus down the line.
But as a panacea for a pandemic, the timing of delivery and availability to the general public are likely to fall far short of many people’s expectations.
