Much has happened in the past few months in the field of pneumococcal vaccines. Too much to cover in a short note so this issue is a bit longer than usual but I think you’ll find it worth the time to go through it. We’ll summarize important data on herd immunity and serotype replacement, shifts in the vaccine industry, and breakthroughs in vaccine financing. Along with these news highlights, we report key findings from the web-based survey we asked you to take during the summer and provide important insights on the affordability of pneumococcal vaccines. And we let you know how to share your thoughts about these key findings.

For our last round of Small Grants funding, we’re pleased to have received over 20 applications. This process has proven to be an effective method of allocating resources to developing country investigators for smaller-scale projects that might previously have gone unfunded. We’re interested to see what exciting work emerges from these proposals.

Last but not least, PneumoADIP’s team has grown. We are pleased to welcome Earl V. Wall, PhD as Director of Strategic Planning and Management and Ellen Lee, MD MPH as Medical Epidemiologist. They bring great skills, experience, and enthusiasm to our team.

IN THIS ISSUE:
1. The U.S. Experience with 7PCV: CDC report on U.S. PCV7 Direct and Indirect Effects and Alaska PCV7 study.
Two important reports on the direct and indirect effects of routine pneumococcal vaccination of children have been published in the past 3 weeks. Both papers come out of the US CDC, one reports the results from surveillance of nearly 20 million people in the general US population and the other reports the results from Alaska, including the health impact in the high incidence Alaska Native populations. The general population results were reported in CDC’s MMWR and the Alaska results in the Vaccine journal.

2. Interview: Dr. Deron C. Burton, the lead author of the CDC report on U.S. PCV7 Direct and Indirect Effects, spoke with PneumoADIP.

3. PneumoADIP Web-Based Survey 2005: Key findings.

4. Vaccine Supply News: Wyeth’s new plant and GSK’s new acquisition.

5. Vaccine Research: Highlights of summer publications.

6. Upcoming Events

Orin Levine Executive Director

Together, the CDC report and the Alaska study provide evidence that in the United States:

• Routine vaccination of young children with PCV7 prevents serious pneumococcal disease among both vaccinated children and their unvaccinated contacts.
• The incidence of invasive pneumococcal disease due to non-vaccine serotypes (i.e., “serotype replacement”) increased following routine vaccination, but at rates that were small relative to the overall declines in invasive disease due to vaccine-types.
• Twice as many cases of serious pneumococcal disease were prevented by the indirect effects of vaccination than by the direct effects of vaccination alone. This finding means that cost-effectiveness analyses that do not include the indirect effects of vaccination will underestimate the health and economic impacts of vaccination.
• Vaccination can protect the most vulnerable, highest risk populations, including those living in rural areas.

Summer, 2005. PneumoADIP conducted a web-based survey during the summer in order to assess the perceptions of the technical community in relation to the issues of financing and pricing of childhood pneumococcal vaccines. We want to thank the many readers of PneumoFOCUS who responded. In sum, the 90 respondents to this survey self-identified themselves as researchers, clinicians, working in industry, in technical agencies, in NGOs, or in other areas. The 9-question survey included questions related to perceptions of the costs of manufacturing pneumococcal conjugate vaccines, expectations for pricing, and awareness of the financing available to developing countries through GAVI’s Vaccine Fund. As promised, here are the top-line findings from the survey responses.

Key findings suggest that finding solution space among country, industry and donors for pneumococcal vaccine introduction is indeed feasible, although not without challenges:

• 71% responded that they thought multi-valent pneumococcal conjugate vaccines can be made affordable to developing countries.
• 50% responded that it costs US$6 or more to manufacture a dose of the licensed 7-valent pneumococcal vaccine. 10% responded that it costs US$20 or more and 20% responded that it costs US$2 or less to manufacture.
• 50% responded that, after 10 years of financing by GAVI, the maximum price per dose that developing countries and their donor partners can sustain is between US$1 and US$2; 30% responded that the maximum price could be between US$3 to $5 per dose; and 20% responded that it could be higher than US$5.
• 77% responded that researchers can influence donors and policy makers in decisions about pneumococcal vaccine introduction.
• 74% responded that companies should expect to make a profit on vaccines that are supplied to developing countries.
• 27% of respondents had a “maximum price” estimate that was equal to or higher than their estimate of the costs of manufacturing.

So, what does all this mean? While most of the respondents were generally optimistic that conjugate vaccines “can be made affordable,” the responses to the individual questions were not always consistent with this optimistic picture. First of all, based on analyses conducted for PneumoADIP, most respondents overestimated the costs of manufacturing multi-valent pneumococcal conjugate vaccines. Second, only 27% of respondents estimated a manufacturing cost that was less than the “maximum” price per dose that countries can sustain. Lastly, only 18% of the respondents answered all 3 of the questions about GAVI fundraising accurately. More often than not, respondents underestimated the amount of funding GAVI had available.

In short, this is very good news indeed. By comparing the perceptions of the community to actual numbers, there is clearly more “solution space” than the technical community generally believes (even though they are generally optimistic people!). Because the technical community tends to overestimate the costs of vaccine manufacturing and to underestimate the amount of financing available to introduce new vaccines like pneumococcal conjugates, the actual differences are actually less than they seem. Also, based on the experience of our colleagues, the respondents were accurate in their assessment that researchers can influence donors and policy-makers.

Do these finding surprise you or are they as you expected? To share your thoughts about these findings with PneumoADIP, click here.

As the field of pneumococcal vaccine continue to develop, PneumoADIP will continue to consolidate key research findings and key news in vaccine financing and supply and share with our colleagues. For a list of current evidence-based information, click here.

Dublin , Ireland – September 8, 2005 . Wyeth formally opened its $US2 billion Grand Castle biotech production facility in South County Dublin, Ireland. According to the press release, this 1.2 million square-foot campus includes a drug development unit, a drug substance site, and a drug production facility. Over the next four years, these facilities will phase into manufacturing its products, including Prevnar. With increased manufacturing capacity, Wyeth has begun to roll-out vaccine in several additional countries, including India and South Africa . Also, according to Wyeth, their vaccine pipeline includes the development of an extended pneumococcal conjugate vaccine containing 13 serotypes.

U.S.A. & Canada – September 7, 2005 . In the press release, GlaxoSmithKline (GSK) announced its acquisition of ID Biomedical. This acquisition brings ID Biomedical’s common protein pneumococcal vaccine candidate into GSK’s early-phase vaccine pipeline. At the tail-end of GSK’s vaccine pipeline, according to its website, GSK is currently preparing to license its 10-valent pneumococcal conjugate vaccine, Streptorix, in 2007.

Review: PCV Impact, Outcomes and Efficacy. This review summarized the outcome and efficacy data from various clinical trials for the 7-valent and 9-valent conjugate vaccines, highlighting the success rate of pneumococcal conjugate vaccines in reducing the incidence of invasive pneumococcal disease. The review also pressed the need to introduce these vaccines into developing countries and cited the PneumoADIP’s critical role in this process. Whitney, Pediatr Infect Dis J. 2005 Aug;24(8):729-30.

Research: Antibiotic Resistance and Genetic Determinants.Streptococcus pneumoniae B-lactam antibiotic resistance is due to the bacterium’s ingenious ability to evade effective drug binding by modifying its key protein targets, particularly the Penicillin Binding Proteins (PBPs). However sequence analysis of PBP domains from S. pneumoniae strains with varying antibiotic resistance showed little genetic variability. This suggests that other genes and perhaps more complex gene interactions are likely to play a role in the intricate mechanisms underlying S. pneumoniae antibiotic resistance. Chesnel et al, Antimicrob Agents Chemother. 2005 Jul;49(7):2895-902.

Epidemiologic Research: HIV, HAART and Pneumococcal Disease. The incidence of invasive pneumococcal disease in HIV-infected patients is reportedly several times higher than in the general population. However widespread use of highly active antiretroviral therapy (HAART) has contributed to a decline in incidence and mortality from opportunistic infections in HIV-infected patients. A recent epidemiological study reveals a decrease in pneumococcal bacteremia in HIV-infected patients, associated with more frequent use of HAART and the 23-valent pneumococcal vaccine. Assessment of the impact of HAART on immune responses to pneumococcal disease is important in developing better vaccine strategies in HIV-infected populations. Grau et al, Arch Intern Med. 2005 Jul 11;165(13):1533-40.

Research: Anatomically Divergent, Genetically Convergent Pneumococcal Strains. Pneumococci bacteria play a dominant role in the pathogenesis of otitis media, or middle ear infection. However the spatial and temporal dynamics of infection remain ambiguous. Novel molecular typing techniques have shown high genetic relatedness between pneumococcal populations originating from the middle ear and upper respiratory regions of children with otitis media, suggesting a common source of infection. These findings support the proposition that middle ear infections are established by identical bacterial clones that colonize the tympanic cavity from the nasopharynx. This work may contribute to the identification of better pneumococcal vaccine strain candidates. Tonnaer et al, J Clin Microbiol. 2005 Jul;43(7):3140-4.

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