Hot topics in vaccination: efficacy, impact and attitudes

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Special article collection features top research in Vaccine from 2018

Advances in the field of synthetic DNA have led to the fastest known development of a vaccine – in this case against Zika virus, going from no vaccine to the clinic in six and a half months. Early studies show it is highly immunogenic, and people receiving the vaccine generated antibodies that, when transferred to mice, protected them from a high dose Zika challenge.

Technologies like this are revolutionizing the field of vaccinology, yet we’re experiencing an unprecedented rejection of vaccines, resulting in the resurgence of vaccine-preventable diseases like measles and mumps, with devastating consequences.

In this special article collection, you can find research that reflects some of the hot topics in vaccine research, including the development and improvement of vaccines against influenza, a meta-analysis of HPV vaccine efficacy at varying doses, as well as insights into attitudes towards vaccination – and what we can do to change them in the era of fake news.

A new approach to the seasonal flu vaccine

Every year, researchers have to work fast to produce a flu vaccine that will protect people from the new strains that are likely to circulate, with the aim of reducing infections, complications and deaths. While the public are most concerned by the appearance of novel H7 or H5 strains like bird flu, seasonal flu is much more of a public health threat, claiming an estimated 80,000 lives and leading to an estimated 900,000 hospitalizations during 2017-2018 in the US alone.

In Asia, new strains of influenza arise through the close interaction of humans, birds, and pigs. Those and other strains that infect humans are detected from around the world and sent to labs every year, and the details are shared publicly so vaccines can be made for that season – those viruses generally appear in Europe and the Americas between August and February. There are four strains that need to be covered by the seasonal flu vaccine: influenza H1N1 and H3N2, and two B strains.

It’s a challenge that’s repeated year after year, starting from scratch each time to match the new strains. Professor David Weiner, Director of the Vaccine & Immunotherapy Center at The Wistar Institute in Philadelphia, USA, and his colleagues wanted to improve the process, and their approach was inspired by the phylogenetic tree of influenza. He explained:

“Abstractly, you can imagine the seasonal flu virus being trapped inside a theoretical space in battle with the human immune system like a person being confined to a room with limited escape options. When blocked by the immune system, the flu virus incorporates changes that help it evade the immune response. However, genetically, it doesn’t have the ability to change everything. Just like the person in the room with only so many exits to choose from, the flu has to keep going back to previous solutions to escape the immune response. This is why new strains appear close to previous ones – 2009 was close to 1918, for example. This unique feature of flu, which I don’t think has been explored fully yet, is a limitation we can exploit in the vaccine.”

In their paper in Vaccine, Dr. Weiner and his colleagues made a vaccine based on sequences derived from the branch points in the phylogenetic tree – four microconsensus spanning regions – with the goal of preventing most new changes in H1 from surprising us. They studied it in mice, ferrets, guinea pigs and monkeys and found they all developed broad immunity and the vaccine offered broad protection – not just from disease but from infection as well.

“We can see that the vaccine would protect historically, though we can’t be certain it will protect in the future,” said Dr. Weiner. “But it makes it easier to cover more ground, and simple to fill in should there be a dramatic change.”

The response to the study has already been positive. “We’ve had a lot of people contact us to talk about this paper,” said Dr. Weiner. “We used it to submit for an NIH grant. Vaccine is one of the most impactful vaccinology journals and it has a wide readership including companies and academics, which is important for translational research like this. Our paper has had good exposure and good coverage, and I believe it will continue to pay dividends.”

Exploring the impact of vaccination

There is more work to be done before the microconsensus flu vaccine can be used in the general population, but as for all vaccines, the work will continue even once it’s licensed. The monitoring of licensed vaccines is vital to ensure their ongoing efficacy and correct use.

Human papillomavirus (HPV) vaccines, for example, were licensed as a three-dose series, but recommendations are for two doses for people who start the vaccination series before age 14 years. There is also increasing interest in possibly single dose vaccination. Dr. Lauri Markowitz, from the Centers for Disease Control and Prevention (CDC) in the US, and colleagues around the world conducted a systematic literature review of HPV vaccine effectiveness with different doses.

In their paper in Vaccine, which was part of the Special Issue “Preventing Cervical Cancer: How much HPV Vaccine do we need?” the team identified 3,787 articles on the topic; 26 were selected according to their criteria and assessed in full, and 14 were included in the review. All of the studies found significant vaccine effectiveness with three doses, 11 with two and six with just one, and most suggested higher effectiveness with more doses.

However, there are many limitations in current post-licensure HPV vaccine effectiveness studies, most biasing against finding effectiveness with fewer doses. Of importance, most persons who received two doses did not receive the doses according to the recommended two-dose schedule.

This kind of research is important for informing vaccine policy. As Dr. Markowitz and her colleagues concluded, “Future effectiveness studies, examining persons vaccinated prior to the onset of sexual activity and using methods to reduce potential sources of bias, can help inform vaccination policy.”

Understanding attitudes to vaccination

The HPV vaccine is one of the field’s big success stories. Now a decade after it was first released, there has been a dramatic reduction in both the circulation of the virus in vaccinated groups, and the incidence of HPV-related cancers.

But vaccines like this are often a victim of their own success: successful vaccines mean the diseases they protect against seem to disappear, making people believe they are no longer needed. Combined with the small but determined anti-vaccination movement, in the era of fake news and social media, this is leading to a resurgence in vaccine preventable diseases like measles, and an increase in people’s risk of infection and death.

How can we turn this around? First we need to understand how people are engaging with information. A study in Vaccine led by Ca' Foscari University of Venice in Italy demonstrated that people’s consumption of vaccine-related content on Facebook is dominated by the echo chamber effect, and their views are polarized over time. Their analysis of 2.6 million users and almost 300,000 Facebook posts over a period of seven years and five months goes a long way to explaining why campaigns to provide accurate information have limited reach on social media.

The authors conclude: “Public health professionals should try to understand the contents of these echo chambers, for example by getting passively involved in such groups. Only then it will be possible to find effective ways of countering anti-vaccination thinking.”

Simply communicating the facts to make people change their minds about vaccination isn’t working; in their commentary in Vaccine, researchers at Bambino Gesù Children’s Hospital in Italy say “To talk better about vaccines, we should talk less about vaccines.” Vaccine communication needs reframing, they say, to focus on the positive, emotional values of vaccination. This will require collaboration between clinicians, vaccine researchers, behavioral scientists, journalists and communication experts, and a research agenda that investigates the effectiveness of different strategies.

In all the noise around vaccination on social media, it pays to remember why effective communication is so important. As the researchers conclude: “We believe that the proposed approach could give a new boost to vaccine confidence, in the interest of the community at large, and of children and their future.”

Read the collection Vaccine

Read more about the studies mentioned and explore others in the new collection. Many of the papers are open access; the others will be free to read until July 30, 2019.

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