Vaccines do work for pandemic flu, says study

Vaccines are successful in preventing pandemic flu and reducing the number of patients hospitalised as a result of the illness, a study led by academics at The University of Nottingham has found.

However, the research -- the most comprehensive review undertaken in this area -- also found that the effectiveness of vaccines can vary depending on the age of the patient.

The work, published in the journal Vaccine, was led by Professor Jonathan Van Tam and Dr Louise Lansbury in the University's Health Protection and Influenza Research Group in collaboration with other scientists in the UK, Japan, Bosnia and the Netherlands.

Professor Van Tam said: ""The 2009 swine flu pandemic was the first in human history when pandemic vaccines have been available worldwide. It's therefore really important to pull all of these data together and ask the question: did these vaccines really work?

"We found that the vaccines produced against the swine flu pandemic in 2009 were very effective in both preventing influenza infection and reducing the chances of hospital admission due to flu. This is all very encouraging in case we encounter a future pandemic, perhaps one that is more severe. Of course, we recognise that it took five to six months for pandemic vaccines to be ready in large quantities; this was a separate problem. However, if we can speed up vaccine production times, we would have a very effective strategy to reduce the impact of a future flu pandemic."

In early 2009, a novel influenza A(H1N1) virus appeared in humans, containing a unique combination of influenza genes which had not previously been identified in animals or people. The first cases were reported in the United States in March 2009 but the new virus spread rapidly to other countries and in June 2009 the WHO declared a pandemic caused by this strain, known as influenza A(H1N1)pdm09, or 'swine flu'.

An estimated 61 million people were infected worldwide. Vaccines against the new strain were developed and rolled out across the world from September to December 2009. The majority of vaccines available contained inactivated A(H1N1)pdm09 influenza virus rather than live virus. Some formulations also contained an 'adjuvant' to strengthen the body's immune response to the vaccine and allow smaller doses of antigen to be used (adjuvanted vaccines).

Many individual studies have looked at how effective the available vaccines were at preventing illness and hospitalisation caused by the pandemic influenza strain but up until now no-one has summarised all the available data. This systematic review and meta-analysis is the most comprehensive summary and offers insight into the relative effectiveness of both adjuvanted and non-adjuvanted vaccines in different age groups.

The researchers found 38 studies published between June 2011 and April 2016 that measured the effectiveness of the inactivated pandemic influenza vaccines, covering a population of more than 7.6m people. Twenty-three of these studies reported results that were suitable for meta-analysis -- a statistical method used to combine the results from multiple individual studies that are broadly similar in terms of vaccine used and types of people in the study and which is statistically more powerful and can provide a more precise estimate of the effect of vaccination than any individual study contributing to the analysis.

Overall, pandemic influenza vaccines were found to be 73 per cent effective at preventing laboratory-confirmed influenza illness and 61 per cent effective at preventing hospitalisation in the population as a whole. However, when the vaccines' effectiveness was examined in different age groups, they were shown to be less effective in adults over 18 years than in children, and effectiveness was lowest in adults over 50 years of age. Adjuvanted vaccines in particular were found to be more effective in children than in adults against laboratory confirmed illness (88 per cent in children versus 40 per cent in adults) and hospitalisation (86 per cent in children versus 48 per cent in adults).

Overall the inactivated pandemic influenza vaccines used in the 2009 pandemic were effective in preventing laboratory-confirmed illness and hospitalisation. Adjuvanted vaccines tended to be more effective than non-adjuvanted vaccines but only in children. The lower effectiveness in older people may be due to them having pre-existing antibodies against A(H1N1)pdm09 from previous exposure to a similar virus, with corresponding lower incidence of the infection in this age group.

The results showed that pandemic influenza vaccines produced globally during the 2009-10 pandemic were largely effective in reducing illness and hospitalisation. The results from the study could be used to help public health officials to plan a more effective response to future pandemics, such as rolling out vaccines at a much earlier time and targeting specific types of vaccines at different age groups.

Cuba’s Effective and Cheap Cholera Vaccine

Dr. Rafael Fando, from Cuba’s National Scientific Research Center, has been working to develop a cholera vaccine since he graduated from medical school in 1993.

This scientific research entity was created 50 years ago, right?

Rafael Fando: Exactly. The center was founded in 1965. It was the first scientific institution of its kind in Cuba, and many of the research centers and researchers working at different institutions around the country emerged from it.

What is the average age of the scientists working at the center?

RF: Around 40 years.

What kind of research is conducted here?

RF: We conduct biomedical research in 3 areas: the development of natural products, environmental studies and biological products designed to prevent infectious diseases.

Why work in the development of a cholera vaccine, when the disease has practically no incidence in Cuba?

RF: It was an idea Fidel Castro had in 1991, when an epidemic broke out in Peru. We were going through the most difficult years of the Special Period economic crisis. The idea came up because no pharmaceutical company was willing to address the issue, because it is not a vaccine that can generate much profit. Several research centers began the work, some with an inactive variant and we with a live, single-dose vaccine.

Cholera vaccines are aimed at poor populations in underdeveloped countries, so it’s ideal for a single dose to do the trick.

Were you a student at the time?

RF: That’s right. I was doing my graduating project at this center, isolating monoclonal antibodies for the cholera toxin. When I graduated, I started working in the development of the vaccine here.

Did you ever imagine you would one day head this research work?

RF: I never imagined it, but it was interesting. We had a team of highly-dedicated people, from veteran researchers to the youngest of the lot, and everyone worked non-stop from 7 am to 9 pm.

Cuba’s vaccine could cost 20 times less than the Swedish one and could be afforded by the poor countries that need it most. Photo: Raquel Perez Diaz

Work on this vaccine has been going for nearly 25 years. Why so long?

RF: Cuba doesn’t have enough resources so as to allow us to quickly develop a vaccine for a disease that is practically non-existent in the country. We’ve made progress whenever there’s been financing for the work.

The first vaccine test candidates were secured in 96 and, that same year, we began clinical trials. We did more tests afterwards. In 2006, we managed to conduct a trial in Mozambique, but the project was later aborted. We resumed it in 2013, when we secured funding to set the costly vaccine assessment system in motion.

When cholera broke out in Haiti and we had some cases in Cuba, we resumed the work, in coordination with the Finlay Institute, so as to obtain experimental vaccine lots. We also worked with the Pedro Kouri Institute, which is responsible for clinical evaluations.

Have you ever received international support?

RF: Never. The funding for this project is fully Cuban, save for the trial conducted in Mozambique, which was co-funded by that country’s Ministry of Public Health.

Why does the World Health Organization (WHO) believe it is important for Haiti?

RF: They are facing a broad cholera epidemic and, coincidentally, the vaccine we’ve been developing has the same serotype as the strain that affects Haiti. The advantage of our vaccine is that, if you administer it properly, it offers people protection against subsequent infections.

How much work still remains before you have a viable vaccine?

RF: We have to complete the phase 2 clinical trials. We would then have to set up a plant that will manufacture enough vaccines. We would also have to pre-qualify the vaccine, that is to say, certify it with the WHO.

We must locate a fairly significant cholera outbreak to assess our vaccine in a phase 3 study, where we can evaluate its safety and effectively.

In our trials, the vaccine has provided 100 % protection against cholera and in 80 % of cases it could prevent the bacterial infection in individuals. This prevents the spread of the disease, acting as a kind of barrier.

Photo: Raquel Perez Diaz

If cholera vaccines already exist, why not use those?

RF: Because those vaccines are aimed at the travelers’ market. A single dose costs 40 euros and you need 2. It’s not a vaccine countries affected by cholera, which are the poorest, can use.

How much would the Cuban vaccine cost?

RF: Our vaccine could compete with India’s, which requires 2 doses and costs US $ 3.70 each. Some 300 thousand doses of the vaccine will be administered in Haiti, for a total of US $3 million, a sum of money that cannot be paid by countries that suffer cholera.

The advantage of our vaccine is that we can offer a better price and, since we can administer it in a single dose, we can spare these countries a vaccination campaign, which is more expensive than the vaccine itself.

Could relations with the United States facilitate some form of collaboration in this field?

RF: It’s going to make academic exchange much easier, without a doubt. In 1999, I traveled to the United States to take part in a congress about cholera, but they’ve denied me a visa every other time I’ve been invited. I hope we can now establish better links and even secure investments to be able to develop this product.

Currently, we can manufacture lots of up to 4000 doses in Cuba, but that is not enough. There are plans of making a small investment aimed at producing 250,000 doses a year, but that would still not be enough. We are planning to set up a manufacturing plant in the Mariel Special Development Zone, so as to secure foreign investment. We would need about US $40 million. With that funding, we could have the vaccine ready in 3 years.

  • Published in Cuba
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