The 2009 swine flu pandemic vaccines were influenza vaccines developed to protect against the pandemic H1N1/09 virus. These vaccines either contained inactivated (killed) influenza virus, or weakened live virus that could not cause influenza. The killed virus was injected, while the live virus was given as a nasal spray. Both these types of vaccine were produced by growing the virus in chicken eggs. Around three billion doses were produced, with delivery in November 2009.
In studies, the vaccines appeared both effective and safe, providing a strong protective immune response and having a similar safety profile to the usual seasonal influenza vaccine.
However, about 30% of people already had some immunity to the virus, with the vaccine conferring greatest benefit on young people, since many older people are already immune through exposure to similar viruses in the past. The vaccine also provided some cross-protection against the 1918 flu pandemic strain. Early results (pre-25 December 2009) from an observational cohort of 248,000 individuals in Scotland showed the vaccine to be effective at preventing H1N1 influenza (95.0% effectiveness [95% confidence intervals 76.0–100.0%]) and influenza-related hospital admissions (64.7% [95% confidence intervals 12.0–85.8%]).
Developing, testing, and manufacturing sufficient quantities of a vaccine is a process that takes many months. According to Keiji Fukuda of the World Health Organization, "There's much greater vaccine capacity than there was a few years ago, but there is not enough vaccine capacity to instantly make vaccines for the entire world's population for influenza." The nasal mist version of the vaccine started shipping on 1 October 2009.
Types Two types of influenza vaccines were available: TIV (flu shot (injection) of trivalent (three strains; usually A/H1N1, A/H3N2, and B) inactivated (killed) vaccine) or LAIV (nasal spray (mist) of live attenuated influenza vaccine.)
TIV works by putting into the bloodstream those parts of three strains of flu virus that the body uses to create antibodies; while LAIV works by inoculating the body with those same three strains, but in a modified form that cannot cause illness.
LAIV is not recommended for individuals under age 2 or over age 49, but might be comparatively more effective among children over age two.
Manufacturing methods For the inactivated vaccines, the virus is grown by injecting it, along with some antibiotics, into fertilized chicken eggs. About one to two eggs are needed to make each dose of vaccine. The virus replicates within the allantois of the embryo, which is the equivalent of the placenta in mammals. The fluid in this structure is removed and the virus purified from this fluid by methods such as filtration or centrifugation. The purified viruses are then inactivated ("killed") with a small amount of a disinfectant. The inactivated virus is treated with detergent to break up the virus into particles, and the broken capsule segments and released proteins are concentrated by centrifugation. The final preparation is suspended in sterile phosphate buffered saline ready for injection. This vaccine mainly contains the killed virus but might also contain tiny amounts of egg protein and the antibiotics, disinfectant and detergent used in the manufacturing process. In multi-dose versions of the vaccine, the preservative thimerosal is added to prevent growth of bacteria. In some versions of the vaccine used in Europe and Canada, such as Arepanrix and Fluad, an adjuvant is also added, this contains squalene, vitamin E and an emulsifier called polysorbate 80.
To make the live vaccine, the virus is first adapted to grow at and then grown at this temperature until it loses the ability to cause illness in humans, which requires the virus to grow at normal human body temperature of . Multiple mutations are needed for the virus to grow at cold temperatures, so this process is effectively irreversible and once the virus has lost virulence (become "attenuated"), it will not regain the ability to infect people. The attenuated virus is then grown in chicken eggs as before. The virus-containing fluid is harvested and the virus purified by filtration; this step also removes any contaminating bacteria. The filtered preparation is then diluted into a solution that stabilizes the virus. This solution contains monosodium glutamate, potassium phosphate, gelatin, the antibiotic gentamicin, and sugar.
A different method of producing influenza virus was used to produce the Novartis vaccine Optaflu. In this vaccine the virus is grown in cell culture instead of in eggs. This method is faster than the classic egg-based system and produces a purer final product. There are no traces of egg proteins in the final product, so it is safe for people with egg allergies.
Previous seasonal vaccine production Prior to the H1N1/09 outbreak, WHO recommended that vaccines for the Northern Hemisphere's 2009–2010 flu season contain an A(H1N1)-like virus, and stocks were made available. However, the strain of H1N1 in the seasonal flu vaccine was different from the pandemic strain H1N1/09 and offered no immunity against it. The US Centers for Disease Control and Prevention (CDC) characterized over 80 new H1N1 viruses that may be used in a vaccine.
Production questions and decisions
Questions There was concern in mid-2009 that, should a second, deadlier wave of this new H1N1 strain appear during the northern autumn of 2009, producing pandemic vaccines ahead of time could turn out to be a serious waste of resources as the vaccine might not be effective against it, and there would also be a shortage of seasonal flu vaccine available if production facilities were switched to the new vaccine. Seasonal flu vaccine was being made as of May 2009. Although vaccine makers would be ready to switch to making a swine flu vaccine, many questions remained unanswered, including: "Should we really make a swine flu vaccine? Should we base a vaccine on the current virus, since flu viruses change rapidly? Vaccine against the current virus might be far less effective against a changed virus – should we wait to see if the virus changes? If vaccine production doesn't start soon, swine flu vaccine won't be ready when it's needed."
The costs of producing a vaccine also became an issue, with some U.S. lawmakers questioning whether a new vaccine was worth the unknown benefits. Representatives Phil Gingrey and Paul Broun, for instance, were not convinced that the U.S. should spend up to US$2 billion to produce one, with Gingrey stating "We can't let all of our spending and our reaction be media-driven in responding to a panic so that we don't get Katrina-ed. ... It's important because what we are talking about as we discuss the appropriateness of spending $2 billion to produce a vaccine that may never be used – that is a very important decision that our country has to make." In fact, a Fairleigh Dickinson University PublicMind poll found in October 2009 that a majority (62%) of New Jerseyans were not planning on getting the vaccine at all.
Before the pandemic was declared, the WHO said that if a pandemic was declared it would attempt to make sure that a substantial amount of vaccine was available for the benefit of developing countries. Vaccine makers and countries with standing orders, such as the U.S. and a number of European countries, would be asked, according to WHO officials, "to share with developing countries from the moment the first batches are ready if an H1N1 vaccine is made" for a pandemic strain. The global body stated that it wanted companies to donate at least 10% of their production or offer reduced prices for poor countries that could otherwise be left without vaccines if there is a sudden surge in demand.
Production timelines After a meeting with the WHO on 14 May 2009, pharmaceutical companies said they were ready to begin making a swine flu vaccine. According to news reports, the WHO's experts would present recommendations to WHO Director-General Margaret Chan, who was expected to issue advice to vaccine manufacturers and the Sixty-second World Health Assembly. WHO's Keiji Fukuda told reporters "These are enormously complicated questions, and they are not something that anyone can make in a single meeting." Most flu vaccine companies can not make both seasonal flu vaccine and pandemic flu vaccine at the same time. Production takes months and it is impossible to switch halfway through if health officials make a mistake. If the swine flu mutates, scientists aren't sure how effective a vaccine made now from the current strain will remain. Rather than wait on the WHO decision, however, some countries in Europe have decided to go ahead with early vaccine orders.
On 20 May 2009, AP reported: "Manufacturers won't be able to start making the [swine flu] vaccine until mid-July at the earliest, weeks later than previous predictions, according to an expert panel convened by WHO. It will then take months to produce the vaccine in large quantities. The swine flu virus is not growing very fast in laboratories, making it difficult for scientists to get the key ingredient they need for a vaccine, the 'seed stock' from the virus [...] In any case, mass producing a pandemic vaccine would be a gamble, as it would take away manufacturing capacity for the seasonal flu vaccine for the flu that kills up to 500,000 people each year. Some experts have wondered whether the world really needs a vaccine for an illness that so far appears mild."
Another option proposed by the CDC was an "earlier rollout of seasonal vaccine," according to the CDC's Daniel Jernigan. He said the CDC would work with vaccine manufacturers and experts to see if that would be possible and desirable. Flu vaccination usually starts in September in the United States and peaks in November. Some vaccine experts agree it would be better to launch a second round of vaccinations against the new H1N1 strain instead of trying to add it to the seasonal flu vaccine or replacing one of its three components with the new H1N1 virus.
The Australian company CSL said that they were developing a vaccine for the swine flu and predicted that a suitable vaccine would be ready by August. However, John Sterling, Editor in Chief of Genetic Engineering & Biotechnology News, said on 2 June, "It can take five or six months to come up with an entirely novel influenza vaccine. There is a great deal of hope that biotech and pharma companies might be able to have something ready sooner."
, a vaccine for H1N1/09 was expected to be available starting in November 2009, with production of three billion doses per year. It was expected that two doses would be needed to provide sufficient protection, but tests indicated that one dose would be sufficient for adults.
, GlaxoSmithKline produced a vaccine made by growing the virus in hens' eggs, then breaking and deactivating the virus, and Baxter International produced a vaccine made in cell culture, suitable for those who have an egg allergy. The vaccines have been approved for use in the European Union.
Testing Initial Phase I human testing began with Novartis' MF59 candidate in July 2009, at which time phase II trials of CSL's candidate CSL425 vaccine were planned to start in August 2009, but had not begun recruiting. Sanofi Pasteur's candidate inactivated H1N1 had several phase II trials planned , but had not begun recruiting.
News coverage conflicted with this information, as Australian trials of the CSL candidate were announced as having started on 21 July, and the Chinese government announced the start of trials of the Hualan Biological Engineering candidate.