Luis Jodar

Streptococcus pneumoniae serotype 19A: Worldwide epidemiology.

ABSTRACT Introduction: Streptococcus pneumoniae causes mucosal and invasive diseases with high morbidity and mortality. Introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) into routine infant immunization programs worldwide resulted in serotype 19A becoming a leading cause of the remaining pneumococcal disease burden in vaccinated and nonvaccinated individuals. This article reviews the impact of the latest generation PCVs (10-valent PCV, PCV10, and 13-valent PCV, PCV13) on serotype 19A. Areas covered: This article covers immune responses elicited by PCV7, PCV10 and PCV13 against serotype 19A and their impact on nasopharyngeal (NP) carriage and disease in vaccinated and unvaccinated populations using data from surveillance systems, randomized controlled trials, and observational studies. Expert commentary: As expected from a PCV containing serotype 19A, PCV13 elicits significantly higher functional immune responses against serotype 19A than PCV7 and PCV10. Higher responses are likely to be linked to both direct impact in vaccinated populations and reductions in 19A NP carriage in children, thus inducing herd protection and reducing 19A invasive pneumococcal disease (IPD) in nonvaccinated children and adults. In contrast, PCV7 and PCV10 have shown mixed evidence of direct short-lived cross-protection and little to no impact on 19A carriage, resulting in continued transmission and disease.

The Evolution of the Meningitis Vaccine Project

Background. In 2001, the Meningitis Vaccine Project (MVP) was tasked to develop, test, license, and introduce a group A meningococcal (MenA) conjugate vaccine for sub-Saharan Africa. African public health officials emphasized that a vaccine price of less than US

From Epidemic Meningitis Vaccines for Africa to the Meningitis Vaccine Project.

0.50 per dose was necessary to ensure introduction and sustained use of this new vaccine. Methods. Initially, MVP envisioned partnering with a multinational vaccine manufacturer, but the target price and opportunity costs were problematic and formal negotiations ended in 2002. MVP chose to become a “virtual vaccine company,” and over the next decade managed a network of public–private and public–public partnerships for pharmaceutical development, clinical development, and regulatory submission. MVP supported the transfer of key know-how for the production of group A polysaccharide and a new conjugation method to the Serum Institute of India, Ltd, based in Pune, India. A robust staff structure supported by technical consultants and overseen by advisory groups in Europe and Africa ensured that the MenA conjugate vaccine would meet all international standards. Results. A robust project structure including a team of technical consultants and 3 advisory groups in Europe and Africa ensured that the MenA conjugate vaccine (PsA-TT, MenAfriVac) was licensed by the Drug Controller General of India and prequalified by the World Health Organization in June 2010. The vaccine was introduced in Burkina Faso, Mali, and Niger in December 2010. Conclusions. The development, through a public–private partnership, of a safe, effective, and affordable vaccine for sub-Saharan Africa, PsA-TT, offers a new paradigm for the development of vaccines specifically targeting populations in resource-poor countries.

Pneumococcal conjugate vaccine use in adults

Background. Polysaccharide vaccines had been used to control African meningitis epidemics for >30 years but with little or modest success, largely because of logistical problems in the implementation of reactive vaccination campaigns that are begun after epidemics are under way. After the major group A meningococcal meningitis epidemics in 1996–1997 (250 000 cases and 25 000 deaths), African ministers of health declared the prevention of meningitis a high priority and asked the World Health Organization (WHO) for help in developing better immunization strategies to eliminate meningitis epidemics in Africa. Methods. WHO accepted the challenge and created a project called Epidemic Meningitis Vaccines for Africa (EVA) that served as an organizational framework for external consultants, PATH, the US Centers for Disease Control and Prevention (CDC), and the Bill & Melinda Gates Foundation (BMGF). Consultations were initiated with major vaccine manufacturers. EVA commissioned a costing study/business plan for the development of new group A or A/C conjugate vaccines and explored the feasibility of developing these products as a public–private partnership. Representatives from African countries were consulted. They confirmed that the development of conjugate vaccines was a priority and provided information on preferred product characteristics. In parallel, a strategy for successful introduction was also anticipated and discussed. Results. The expert consultations recommended that a group A meningococcal conjugate vaccine be developed and introduced into the African meningitis belt. The results of the costing study indicated that the “cost of goods” to develop a group A – containing conjugate vaccine in the United States would be in the range of US

Effectiveness of 13-Valent Pneumococcal Conjugate Vaccine Against Hospitalization for Community-Acquired Pneumonia in Older US Adults: A Test-Negative Design

0.35–

Rethinking number-needed-to-vaccinate for pneumococcal conjugate vaccines in older adults: Current and future implications

1.35 per dose, depending on composition (A vs A/C), number of doses/vials, and presentation. Following an invitation from BMGF, a proposal was submitted in the spring of 2001. Conclusions. In June 2001, BMGF awarded a grant of US

A public health evaluation of 13-valent pneumococcal conjugate vaccine impact on adult disease outcomes from a randomized clinical trial in the Netherlands

70 million to create the Meningitis Vaccine Project (MVP) as a partnership between PATH and WHO, with the specific goal of developing an affordable MenA conjugate vaccine to eliminate MenA meningitis epidemics in Africa. EVA is an example of the use of WHO as an important convening instrument to facilitate new approaches to address major public health problems.

Post hoc analysis of the efficacy of the 13-valent pneumococcal conjugate vaccine against vaccine-type community-acquired pneumonia in at-risk older adults

ABSTRACT Streptococcus pneumoniae is a leading cause of illness and death in adults. A polysaccharide vaccine has been available for over 30 years, but despite significant use, the public health impact of this vaccine has been limited. The 13-valent pneumococcal conjugate vaccine (PCV13) has been licensed by the US Food and Drug Administration and other international regulatory authorities with the assumption that induction of a T cell–dependent immune response and noninferior immunogenicity to vaccine antigens when compared with the polysaccharide vaccine would be important to satisfy a significant unmet medical need. PCV13 efficacy against vaccine-type pneumococcal community-acquired pneumonia was confirmed in a large randomized controlled trial in older adults and its use is now increasingly recommended globally.

Decision-making for PCV in adults

Our study demonstrated real-world, direct effectiveness of 13-valent pneumococcal conjugate vaccine against vaccine-type community-acquired pneumonia following introduction into a routine immunization program among adults aged ≥65 years, many of whom had immunocompromising and chronic medical conditions.

Response to Mungall et al. letter to the editor on Streptococcus pneumoniae serotype 19A: worldwide epidemiology. Expert review of vaccines 2017;16(10):1007–27

BACKGROUND Number-needed-to-vaccinate (NNV) is increasingly used to inform decisions about vaccine use, but it is not calculated uniformly across studies. This study compared two methodologies for calculating NNV with 13-valent pneumococcal conjugate vaccine (PCV13) to prevent one case of community-acquired pneumonia (CAP) among US adults aged ≥65years: (i) using one-year absolute rate differences as was originally performed by the Centers for Disease Control and Prevention (CDC) and (ii) using absolute risk reduction over 5years. METHODS We constructed a hypothetical fixed cohort of 200,000 adults aged ≥65years equally separated into PCV13-vaccinated and PCV13-unvaccinated groups. We incorporated the same conservative assumptions used by CDC in 2014 regarding annual incidence of hospitalized (1375 per 100,000) and outpatient (2010 per 100,000) CAP, the initial (2014) proportion of adult PCV13-type CAP (10%), and PCV13 efficacy against vaccine-type CAP (45%). To model PCV13 impact over time, we assumed annual mortality was 5% for both groups, the percentage of adult PCV13-type CAP declined annually due to pediatric herd effects, and PCV13 efficacy did not wane over 5years. RESULTS Among adults aged ≥65years, NNV with PCV13 to prevent one hospitalized and one outpatient case of CAP as originally calculated by CDC in 2014 were 1620 and 1110, respectively. Accounting for 5-year cumulative effects, NNV with PCV13 to prevent one hospitalized and one outpatient case of CAP over 5years were 576 and 394, respectively. These revised NNV estimates are roughly one third of initial estimates in which cumulative effects were ignored. NNV to prevent any CAP (inpatient or outpatient) over 5years with one PCV13 dose was 234. CONCLUSION Accounting for cumulative preventive effects of PCV13 vaccination over time is critical. Failing to do so, even when using conservative disease burden parameters, can grossly underestimate the public health impact of adult PCV13 use.