Rotavirus Vaccines — A New Hope

Friday, 24th of March 2017

Rotavirus Vaccines — A New Hope

Mathuram Santosham, M.D., M.P.H., and Duncan Steele, Ph.D.

N Engl J Med 2017; 376:1170-1172March 23, 2017DOI: 10.1056/NEJMe1701347

Rotavirus gastroenteritis is the leading cause of diarrhea-associated hospitalization and death in children younger than 5 years of age,1 with more than 85% of the approximately 200,000 annual rotavirus deaths occurring in Africa and Asia.2 Since improvements in water, sanitation, and hygiene do not prevent rotavirus transmission, as they do with the spread of bacterial enteropathogens, the implementation of a rotavirus vaccine is essential to prevent death and complications from childhood diarrhea.

Two rotavirus vaccines — Rotarix (an attenuated G1P8 rotavirus manufactured by GlaxoSmithKline) and RotaTeq (containing five human–bovine reassortant rotaviruses, manufactured by Merck), attained prequalification by the World Health Organization (WHO) in 2008, which paved the way for UNICEF vaccine procurement through the financing mechanisms of the Gavi Alliance. These vaccines, which have been introduced in 42 Gavi-eligible countries and in 6 countries that have been designated as low-income and middle-income, have had a major effect on rotavirus deaths and hospitalizations in all settings.3

However, the uptake of rotavirus vaccines has slowed for various reasons, including supply constraints, high cost, and programmatic concerns for national immunization programs, particularly cold-chain capacity.4 Gavi countries have predominantly selected the attenuated G1P8 rotavirus vaccine,5 which has a smaller vaccine vial size and comes with a vaccine vial monitor for temperature monitoring. The two approved rotavirus vaccines have a liquid ready-to-use formulation. However, issues of cost of the vaccine and vaccine supply remain.

With Gavi support, low-income countries can procure rotavirus vaccines with a minimal copayment of 40 cents (in U.S. currency) per course, and Gavi cofinances the remainder of the UNICEF price (which ranges from $4.50 to $10.50). Low-income and middle-income countries, which are not Gavi-eligible, pay substantially higher costs for rotavirus vaccines.5 Gavis principles for vaccine-supply security emphasize the need for multiple manufacturers in the market to drive down prices while establishing sufficient vaccine supply. This protocol will become more critical as countries transition from Gavi support owing to socioeconomic development.

Fortunately, the situation is improving. In 2013, an indigenously developed rotavirus vaccine (ROTAVAC, Bharat Biotech International) was licensed in India and has been introduced in the routine childhood immunization program in four Indian states, with expanded rollout expected this year. This vaccine is under consideration for WHO prequalification, which would make it eligible for UNICEF procurement and Gavi subsidy. Bharat Biotech has committed to a cost of approximately $3.00 per course for global public markets.

In this issue of the Journal, Isanaka and colleagues6 document the safety and efficacy of an oral bovine rotavirus pentavalent vaccine (BRV-PV) developed by Serum Institute of India. The vaccine, which the investigators evaluated in an impoverished setting in Niger, had a reported efficacy of 66.7%,6 which is similar to that of other licensed rotavirus vaccines in similar settings. Efficacy data from an Indian study are pending. Despite this modest efficacy, the absolute public health benefits of vaccination are large, given the tremendous disease burden. Estimates suggest that rotavirus vaccines have the potential to prevent 2.46 million childhood deaths and 83 million disability-adjusted life-years during the period from 2011 through 2030.7

The authors describe a rotavirus vaccine that is thermostable for 24 months at 37°C and for 6 months at 40°C, which may provide advantages for vaccine delivery in remote areas where cold-chain capacity is limited. However, this vaccine is freeze-dried, and practitioners in many countries may prefer other rotavirus vaccines that have liquid all-in-one formulations to simplify programmatic considerations. The projected cost of this heat-stable vaccine falls between the Gavi prices for the two currently used vaccines. The availability of vaccines from several manufacturers will increase global supply.

During the past three decades, remarkable progress has been made in reducing mortality from diarrheal disease, but the goal of ending such deaths cannot be achieved without aggressive implementation of a comprehensive approach to diarrhea prevention and treatment, including providing access of rotavirus vaccines to every child regardless of economic status. Increased availability of low-cost, programmatically suitable vaccines in abundant supply will be key to achieving this goal.

Disclosure forms provided by the authors are available with the full text of this editorial at NEJM.org.

This editorial was updated on March 23, 2017, at NEJM.org.

SOURCE INFORMATION

From the Department of Pediatrics, Johns Hopkins University, and the Department of International Health, International Vaccine Access Center, and Center for American Indian Health, Johns Hopkins Bloomberg School of Public Health — all in Baltimore (M.S.); and the Bill and Melinda Gates Foundation, Seattle (D.S.).