In 1962, the virus responsible for rubella was isolated by two independent research groups and vaccine development began following this discovery.⁽¹⁾ Also in 1962, Merck scientists isolated a strain of rubella, the Benoit strain, with the intent of developing a killed-virus rubella vaccine. In 1965, however, they decided that a live-virus vaccine would be the best option. This vaccine was developed using duck embryos, as chicken embryo cells proved to be an unsuitable culture medium for rubella vaccine development.⁽²⁾

At the same time, scientists at the Division of Biologics Standards (DBS) were also experimenting with a live attenuated rubella vaccine using bovine kidney cells. In 1966, their vaccine, HPV-77, had been tested on animals and a small number of children.⁽³⁾

In the late 60s, Merck began testing its experimental duck embryo vaccine, and in 1969, Meruvax (HPV-77:DE-5) was licensed for use in people 12 months of age and older. The CDC's Advisory Committee on Immunization Practices (ACIP) recommended the use of rubella vaccine in April 1969, prior to the vaccine's licensure. The vaccine, however, was not developed because rubella was considered a serious disease, but rather because of its impact on the developing infant.⁽⁴⁾

Within a year, two more rubella vaccines, Rubelogen or HPV-77:DK-12 (developed from dog kidneys) and Cendevax or GMK-3:RK53 (developed from rabbit kidneys), also received approval for use.⁽⁵⁾

In August 1970, 15 months after the first rubella vaccine was approved, the CDC reported receiving numerous reports of arthralgia and arthritis in children after administration of the vaccine. Although noting that prelicensure clinical trials reported joint problems in children occurring in less than 5 percent, health officials stated that “with extensive use since licensure, many areas have been alarmed by a greater frequency and severity of reactions than had been expected.”⁽⁶⁾

This report also noted that most side effects usually resolved within one to ten days; however, in some cases joint pain persisted and children required hospitalization for evaluation of rheumatoid arthritis or rheumatic fever.⁽⁷⁾

Children vaccinated with the dog kidney-derived rubella vaccine (HPV-77:DK-12) had a significantly higher rate of joint reactions than children vaccinated with the duck embryo-derived vaccine (HPV-77:DE-5). Other serious events reported after rubella vaccination included transverse myelitis, high fever, ataxia, polyneuritis, aseptic meningitis, temporary paralysis, convulsions, and death.⁽⁸⁾ HPV-77:DK-12 was voluntarily withdrawn from the market in 1973.⁽⁹⁾

In 1971, the measles-mumps-rubella (MMR) vaccine was approved, combining Merck's rubella vaccine, HPV-77:DE-5, with the measles and mumps vaccine. Other combination rubella vaccines were also approved in the 70s, including a mumps-rubella vaccine (Biavax) and a measles-rubella vaccine (MR-Vax).

In the 60s, the Wistar Institute in Philadelphia developed a rubella vaccine, RA27/3, from aborted fetal cells.⁽¹⁰⁾ The vaccine was tested outside the United States in the late 60s, and by the early 70s, it was licensed for use in several countries, including Britain and Australia.^(11-12)

In 1978, Merck decided to license the rubella vaccine RA27/3 in the United States and to discontinue use of the rubella vaccine HPV-77:DE-5.⁽¹³⁾ The RA27/3 rubella vaccine was licensed in January 1979 and replaced all previously available rubella vaccines.⁽¹⁴⁾ In 1979, a single dose of rubella vaccine was recommended for all children 12 months of age and older. In addition, ACIP emphasized the need to ensure that women of childbearing age receive the vaccine or have evidence of immunity from previous exposure to the virus.⁽¹⁵⁾