Hitting the bull's eye for pandemic flu vaccine development

In this month's Lancet Infectious Diseases, a commentary by Sambhara, Bridges, and Poland offers an update on progress toward pandemic influenza vaccine development in the wake of the licensure of Sanofi Pasteur's pre-pandemic vaccine this spring.

The title of the short commentary sums up the authors' assessment: "H5N1 vaccine hits the target, but not the bull's eye." (free abstract). Complementing this metaphor is a graphic which illustrates the specific areas that need to be addressed to produce the "ideal pre-pandemic vaccine." Such a vaccine would be safe (of course), require a single dose with a small amount of antigen, provide long-lasting immunity, and be stable (i.e., capable of remaining potent even if stored for some time).

Given that the Sanofi Pasteur vaccine licensed in April falls far short of these goals, the authors advocate directing research efforts toward these aims in particular.

Speaking of pandemic influenza research, WHO posted on their website late last week a series of tables summarizing the impressive number of vaccine candidates for which clinical trials are underway. As the tables show, while H5N1 is properly commanding the overwhelming majority of attention of late, it is not the only influenza strain with pandemic potential that has attracted the interest of researchers.

With respect to pandemic planning in the U.S., another update was issued late last week by HHS secretary Michael Leavitt. Here's the full report as well as coverage from CIDRAP News. In a brief section on vaccines, the report states that the current pre-pandemic stockpile includes sufficient doses for 6 million people, with a 5-year goal of building enough capacity to produce vaccine for all Americans within six months of 'the' pandemic virus' first appearance.

Research shows potential of edible vaccines

A potentially promising new strategy for vaccine delivery was highlighted in last week's edition of the Proceedings of the National Academy of Sciences (PNAS). In a paper by Nochi and colleagues, "Rice-based mucosal vaccine as a global strategy for cold-chain- and needle-free vaccination," (free abstract), the authors report on favorable immune responses in mice caused by rice genetically-engineered include a vaccine against cholera.

An editorial in the same issue of PNAS ("Vaccines are for dinner,") expresses great optimism about the potential for the Nochi, et al., method to address many of the logistical obstacles that hamper large-scale vaccination efforts, particularly the need to keep traditional vaccines refrigerated at all times from manufacture to delivery (known as the 'cold chain') and the difficulties of needle-based vaccination programs around the world.

Last week's issue of The Economist picked up the story -- "A new health food" -- providing a far more accessible summary of Nochi, et al.'s research for a lay audience.

It is an interesting and potentially important set of research findings, but as with most early-stage research, the journey to a viable human therapy employing rice-based vaccines is, at best, a decade or longer away.

Also in the news: new meningitis vaccine?; ethics of clinical trials

Two other odds-and-ends appearing in our inbox this week:

-- An AP story from late last week proclaims, "New meningitis shot could end fatal epidemics." Not surprisingly, "could" is very much the key word in that headline. As the story points out, the positive data being announced comes from a clinical trial of only 600 toddlers in Africa, and the successful introduction of the vaccine candidate is, at best, years away. More depressing, but no doubt accurate, is this point from the story:

"Even if the new vaccine becomes available, experts think there will be a lag of about 15 years before the majority of Africa’s at-risk population can be vaccinated."

Of course, this 'lag' is present for the introduction of any new vaccine in the developing world, often (as is the case for rotavirus and HPV vaccines) the parts of the world where the greatest vaccine-related benefit is possible.

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-- Speaking of vaccine research and testing in the developing word, the June 21 issue of Vaccine includes a paper titled, "Ethical considerations related to the provision of care and treatment in vaccine trials." (subscription required). Written by Daniel Tarantola, Ruth Macklin, and colleagues, the paper summarizes a meeting exploring the long-disputed question of the type and level of care due to research subjects in the developing world (where the standard of care is typically quite different from the home countries of research sponsors.)

Those looking for a clear recommendation will not find it here. The authors recommend "a structured approach" to decision-making, meaning, "a consultative process with trial communities and other stakeholders in research [that] will ensure that the needs and legitimate expectations of trial participants are appropriately met, obligations towards them are delivered and, as a result, ethical research is facilitated in the interest of public health."

Legal fears block vaccine research for pregnant women, newborns

That's the topic of this story in Friday's Baltimore Sun -- "Pregnant Pause." It examines the potential for a vaccine against Group B Streptococcus -- which affects thousands of newborns annually -- and the (seemingly justifiable) reluctance of the pharmaceutical industry to pursue a vaccine against it.

Why? Among other reasons, the story points to the regulatory difficulties of testing new product in pregnant women and newborns and the extreme legal vulnerability the companies would face if allegations of safety concerns come to light (real or alleged) even after a potential vaccine was licensed.

The story goes on to outline how legal worries influence physician attitudes regarding pertussis and influenza vaccination for pregnant women, contrary to the recommendations of the scientific and medical communities. It's a very interesting story for those thinking about how science, law, and policy interact.

Update on HIV Vaccine Research Strategies

Despite the many challenges facing the development of a safe and effective HIV vaccine (many of which we've discussed previously), we continue to be interested observers in the status of HIV vaccine research, cognizant of the incredible benefits a vaccine would bring.

The latest New England Journal of Medicine includes a review article by NIAID Director Dr. Anthony Fauci and researcher Dr. Margaret Johnston titled "An HIV Vaccine -- Evolving Concepts."

It's a science-laden paper, but its conclusion reflects the increasingly modest hopes for a potential first-generation HIV vaccine. Johnston and Fauci describe a different type of vaccine, one that would alter the common understanding of the protection vaccines provide and create additional implementation concerns along with the potential for tremendous benefits...

" A vaccine that conforms to the classic paradigm of viral vaccines remains the goal of efforts to develop an HIV vaccine. Such a vaccine would induce immune responses that prevented the establishment of HIV infection by clearing virus before latent viral reservoirs were produced. This goal may not be realized with first-generation vaccines. The development of an HIV vaccine may diverge from the classic paradigm for viral vaccines. There is optimism that even a less-than-perfect vaccine could benefit both individual recipients and the at-risk community. By blunting the initial burst of viremia and reducing virus levels, such a vaccine could prolong the disease-free period and also reduce transmission. If licensed, such a vaccine will have to be delivered as part of a comprehensive, multifaceted, prevention program."

Positive data on Hepatitis E vaccine research

Regular readers are aware of our discomfort about reporting on news of vaccines years away from licensure, at best. But when the New England Journal of Medicine decides to include results of Phase I or II clinical trials, it's generally worth noting.

That's the case for the most recent issue of NEJM, which published a paper on the "Safety and Efficacy of a Recombinant Hepatitis E Vaccine." Hepatitis E, more information about which can be found here and here, is quite rare in the United States and is not known to cause chronic conditions. Far more common, of course, are hepatitis A, B, and C (with vaccines available for the first two). Hep E does, however, lead to outbreaks in many parts of the world, particularly in Asia.

The trial reported on here included nearly 1800 volunteers from the Army of Nepal, a population at high risk of contracting the virus. The result: the candidate vaccine's efficacy was 95.5%. No serious safety concerns were identified.

Included in the same issue of NEJM was an editorial titled "Hepatitis E Vaccine -- Ready for Prime Time?"