I wanted to build on the editorial topic of vaccines in this issue of Contract Pharma and discuss how the whole lifecycle from the design (adjuvant and antigen choices), to production, to patient visit all influence the utility of vaccines in actual practice. It’s clear that not frequently facing horrific diseases (such as polio, smallpox, measles, etc.) is a major factor in some proportion of the population avoiding vaccinations for a host of preventable diseases. The public is not equipped for good decision-making when facing low-probability events; In fact in a salient research study, homeowners in California were more likely to buy earthquake insurance AFTER experiencing property damage and destruction from an earthquake—rather than insuring themselves against the risk. Make no mistake: with vaccination this isn’t just a personal choice—vaccination works by the process of herd immunity, which requires a majority of the population to be inoculated for the protective effects to be elicited. According to the Centers for Disease Control and Prevention (CDC), the annual fatality rate for seasonal influenza is between 3,000-49,000 in the United States alone. If we look to worldwide estimates of annual influenza deaths (World Health Organization), the annual estimates are between 250,000-500,000. 

Generally, a lack of understanding is the reason why vaccinations are avoided—the safety profile of vaccines is extraordinarily high, and in fact, most individuals who avoid them because of concerns that they may have an egg allergy may be misguided—a research study from Japan in 2000 showed that the most potent immunogenic components of vaccines are related to gelatin (the IgE antibodies to gelatin more specifically), and not the egg components at all.

The 2013-2014 season trivalent influenza vaccine had an efficacy of about 61% [95% confidence interval: 52% – 68%]. There are many different factors which are related to the efficacy, such as the immunologic status of the individual, genetic response to the vaccine antigen and adjuvant, the infective vectors encountered by each individual, local illness density, and so on.

A recent small research trial (N = 700) of a vaccine for avian flu (H7N9) suggested that the adjuvant (MF59) was strongly correlated with an improved protective effect (p < .05) —in fact, with the adjuvant the efficacy was about 59%, and without the adjuvant, the efficacy was negligibly low. Let me explain how this is typically measured: An assay called a hemagglutinin inhibition antibody test (HAI or HI) is performed, and a threshold of 40 is used to identify the point at which a sufficient immune response is attained. The CDC suggests that “serum HI antibody titers of 40 are associated with at least a 50% reduction in risk for influenza infection or disease in populations.” Both the control group (antigen only) and treatment group (antigen plus adjuvant) were given two inoculations spaced 21 days apart. No relevant antibody response was generated in the antigen-only (control) groups, but the efficacy mentioned above (59%) was achieved by the antigen plus adjuvant. Interesting too was the fact that the treatment groups administered the antigen plus adjuvant in one of the inoculations (antigen only in the second 21 days later) attained similar protective antibody levels to the group which received antigen plus adjuvant in both inoculations—This provides some evidence to suggest that adjuvant-sparing and antigen-sparing paradigms could be used in cases of rapid need or pandemic and could have the potential to offer robust protection. H7N9 for example at the moment doesn’t spread readily from person-to-person, however in the 452 confirmed cases, there was a 37% fatality rate. Being able to improve the profile of efficacy through robust production methods and enhanced patient compliance can go a long way to protecting the public.

One of the most impactful factors as to whether individuals get vaccinated is a strong recommendation from their physician. In fact, in statistics gathered over the use of the shingles vaccine, Zostavax, uptake rate of the vaccine was strongly associated with physician interaction—in a study by Opstelten et al., the most important factor associated with patients not getting the shingles vaccine was lack of strong physician recommendation—and that was even if it was offered free with a seasonal flu vaccine. Even then, that physician:patient interaction isn’t done in a vacuum—hence the power of direct-to-consumer advertising of drug treatments. So how do physicians get reliably notified of what to mention? One way is by reminders given through their electronic health record (EHR) system; Chaudhry et al. found that physician reminders were associated with increases in vaccine use of 43% and 54% at two clinics.

As with all of the challenges we address across our industry, vaccination (from development, production, and through to public use) is a multi-factorial effort and needs our best data and attention to make impactful gains for the benefit of the public.

---

Ben Locwin, PhD, MBA
Healthcare Science Advisors

Ben Locwin, PhD, MBA is President of Healthcare Science Advisors and writes the Clinically Speaking column for Contract Pharma. He is an author on a wide variety of scientific topics. He is also a frequent speaker and consultant for a variety of industries including behavioral and psychological, food and nutrition, pharmaceutical, and academic. Follow him at @BenLocwin.