[Table of Contents]

Volume: 23S4 - May 1997

Canadian National Report on Immunization, 1996

13. New Vaccines on the Horizon

Many more vaccines, such as conjugate pneumococcal and meningococcal vaccines, will appear in the coming years. Some will likely be available in a few years, thanks to the development of new technologies. Three products deserve special mention because of their recent or possible short-term availability and/or their availability in other countries, as well as their potential impact on child health: acellular pertussis vaccines, varicella vaccine, and rotavirus vaccines. The use and availability of the hepatitis A vaccine will not be elaborated upon. Although it is an extremely safe and efficacious vaccine, its use is more limited to high-risk groups; it is not, nor is it likely to be, recommended for routine use.

13.1 Acellular pertussis vaccines

Acellular pertussis vaccines (APVs) contain purified inactivated components of Bordetella pertussis. Several APVs have been developed with different components in varying concentrations, but all contain pertussis toxin (PT) and usually filamentous hemagglutonin. Some have been in widespread use in Japan for primary immunization of children > 2 years of age for over 15 years and for infants > 3 months of age since 1988.  In the United States, APVs were first licensed in 1992 for the fourth and fifth booster doses in children 15 months to 6 years of age. In Canada, between March and July 1996, three APVs were licensed to be used as booster doses in children from 15 months to 6 years of age. They include: Acel-P^TM (Wyeth-Ayerst Canada Inc.), a monovalent APV; ACEL-IMUNE^TM (Wyeth-Ayerst Canada Inc.), an APV combined with diphtheria and tetanus toxoids; and TRIPACEL^TM (Connaught Laboratories Ltd.), an APV combined with diphtheria and tetanus toxoids. In December 1996, two APVs combined with diphtheria and tetanus toxoids (Connaught Laboratories Ltd. and SmithKline Beecham Pharma Inc.) were licensed for primary series in infants. At the recent National Immunization Conference, Connaught Laboratories Ltd., SmithKline Beecham Pharma Inc., Wyeth-Ayerst Canada Inc., and North American Vaccine Inc. indicated that they have applied for licensing of other combination products or intend to do so. Licensing of more combination products is expected in the foreseeable future.

Generally, reactogenicity is less than that reported following the use of the whole-cell pertussis vaccine. Immunogenicity compares favourably with whole-cell vaccines tested. Efficacy of these products as fourth and fifth doses, especially in regard to the whole-cell vaccines used for the primary series in Canada, is not known.

From 1990 to 1995, seven independent field trials of APVs were conducted in Germany (three trials), Italy (one trial), Senegal (one trial), and Sweden (two trials) for primary immunization in infants. Estimated vaccine efficacies were generally greater or more favourable than the whole-cell vaccines, depending on the whole-cell vaccine product compared. Licences were subsequently granted in several European countries for primary immunizations. In the United States, the Food and Drug Administration (FDA) licensed Tripedia^® (Connaught Laboratories Inc.) in 1996 for use in infants and children ³ 2 months of age for the primary series. As new data become available and additional licenses are granted in Canada, NACI will be recommending expanded indications. The present use of these products requires multiple injections for simultaneous administration of IPV, Hib, and hepatitis B vaccines. Data on the safety and immunogenicity of combined injections are not available as yet.  Products combined with inactivated polio and Hib vaccine may become available in the near future.

It is likely that acellular vaccines will be more efficacious than the whole-cell vaccine currently used in Canada. Although the pertussis disease-reduction target will not be achieved on time, the general use of these new products will likely allow Canada to quickly correct the situation. In preparation for the incorporation of APVs for routine administration, a cost-benefit study was contracted out by the Division of Immunization, LCDC. Its results are favourable to the use of the new APVs.

13.2 Varicella vaccines

Varicella (chickenpox) is usually a benign disease, generally experienced by 90% of people; however, it can be severe in immunocompromised individuals. Herpes zoster is also a local manifestation of reactivated, latent varicella infection in the dorsal root ganglia; it occurs in 35% of individuals.

Currently no varicella vaccines are licensed in Canada and it is unlikely that a vaccine will be available for routine use within the next 2 years. A safe, effective, live, attenuated varicella vaccine against varicella zoster was licensed in 1995 in the United States. The American Academy of Pediatrics recommended varicella vaccine for universal use in early childhood and immunization in older adolescents. The recommendation was based on the frequency of serious complications and deaths after mild varicella, the excess cost to the family and society incurred by varicella infection, and the safety and efficacy of the vaccine. Routine use of the vaccine was reported to result in savings of $384 million per year in the United States⁽³³⁾.

However, the Canadian public and health-care providers do not perceive varicella as a severe disease. It does not present a burden to the public-health community. Health-care providers are not completely convinced by the cost-benefit analysis, although savings are great from a societal perspective. Seroconversion in healthy children is 90% versus 87% in leukemic children and 94% in healthy adults. The immunity conferred by the vaccine is considered to be probably long-term. This vaccine may also reduce the risk of herpes zoster, at least in the short term. Reported adverse events include rash, usually maculopapular rather than vesicular, with < 50 spots in 4% to 10% of recipients; injection-site lesions, swelling, pain, and systemic reactions are rare. The vaccine currently used in the United States is difficult to handle because it has to be frozen at all times (below -15^o C). A similar vaccine has been licensed in Japan, Korea, and several European countries. A new more heat-stable vaccine has been developed. In Canada, varicella vaccine can be obtained from manufacturers for compassionate use in emergency situations. Varicella has been monitored through IMPACT and a Canadian cost-benefit study of the potential use of the vaccine will likely be implemented in 1997.

When a vaccine becomes available for routine use in Canada, it will be important to have a common approach across the various jurisdictions. Significant but partial coverage of children may result in older persons (who are at higher risk for complications) being exposed and a shift in the epidemiology of the disease.

13.3 Rotavirus vaccines

Rotavirus infections are an important cause of gastroenteritis in children < 5 years of age.  In the United States, where data are available, these infections are an important cause of dehydration and hospitalization. They result in an estimated 55,000 hospitalizations per year due to dehydration; however the number of related deaths is very limited (300 in 1985). No vaccines are licensed in Canada or the United States. Advances toward development of a successful rotavirus vaccine have been slow. A variety of live attenuated vaccines have been developed including animal rotavirus reassortment strains and temperature-sensitive human rotavirus mutants. Efficacy of candidate vaccines is still under evaluation.

It is likely that the first vaccines adopted for widespread clinical trials will be the multivalent, live, attenuated reassortant vaccines that seem to confer around 50% protection against any diarrhea. They are significantly more effective (around 80%) against severe gastroenteritis and virtually 100% efficacious against dehydration. Vaccines are unlikely to become available on the market before a few years.

Currently, epidemiologic data on rotavirus infections in Canada are almost totally lacking. To prepare for the potential introduction of this vaccine, IMPACT is assessing the burden of the disease through specific surveillance of rotavirus infections. A Canadian cost-benefit analysis will hopefully be conducted in the near future.

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