Pontifical Academy for Life, June 5th, 2005
The matter in question regards the lawfulness of production, distribution and use of certain vaccines whose production is connected with acts of procured abortion. It concerns vaccines containing live viruses which have been prepared from human cell lines of foetal origin, using tissues from aborted human foetuses as a source of such cells. The best known, and perhaps the most important due to its vast distribution and its use on an almost universal level, is the vaccine against Rubella (German measles).
Rubella and its vaccine
Rubella (German measles) 1E. Banatvala, D.W.G. Brown, Rubella, The Lancet, 3rd April 2004, vol. 363, No. 9415, pp.1127-1137 is a viral illness caused by a Togavirus of the genus Rubivirus and is characterized by a maculopapular rash. It consists of an infection which is common in infancy and has no clinical manifestations in one case out of two, is self-limiting and usually benign. Nonetheless, the German measles virus is one of the most pathological infective agents for the embryo and foetus. When a woman catches the infection during pregnancy, especially during the first trimester, the risk of foetal infection is very high (approximately 95%). The virus replicates itself in the placenta and infects the foetus, causing the constellation of abnormalities denoted by the name of Congenital Rubella Syndrome. For example, the severe epidemic of German measles which affected a huge part of the United States in 1964 thus caused 20,000 cases of congenital rubella 2Rubella, Morbidity and Mortality Weekly Report, 1964, vol. 13, p.93. S.A. Plotkin, Virologic Assistance in the Management of German Measles in Pregnancy, JAMA, 26th October 1964, vol.190, pp.265-268, resulting in 11,250 abortions (spontaneous or surgical), 2,100 neonatal deaths, 11,600 cases of deafness, 3,580 cases of blindness, 1,800 cases of mental retardation. It was this epidemic that pushed for the development and introduction on the market of an effective vaccine against rubella, thus permitting an effective prophylaxis against this infection.
The severity of congenital rubella and the handicaps which it causes justify systematic vaccination against such a sickness. It is very difficult, perhaps even impossible, to avoid the infection of a pregnant woman, even if the rubella infection of a person in contact with this woman is diagnosed from the first day of the eruption of the rash. Therefore, one tries to prevent transmission by suppressing the reservoir of infection among children who have not been vaccinated, by means of early immunization of all children (universal vaccination). Universal vaccination has resulted in a considerable fall in the incidence of congenital rubella, with a general incidence reduced to less than 5 cases per 100,000 livebirths. Nevertheless, this progress remains fragile. In the United States, for example, after an overwhelming reduction in the number of cases of congenital rubella to only a few cases annually, i.e. less than 0.1 per 100,000 live births, a new epidemic wave came on in 1991, with an incidence that rose to 0.8/100,000. Such waves of resurgence of German measles were also seen in 1997 and in the year 2000. These periodic episodes of resurgence make it evident that there is a persistent circulation of the virus among young adults, which is the consequence of insufficient vaccination coverage. The latter situation allows a significant proportion of vulnerable subjects to persist, who are a source of periodic epidemics which put women in the fertile age group who have not been immunized at risk. Therefore, the reduction to the point of eliminating congenital rubella is considered a priority in public health care.
Vaccines currently produced using human cell lines that come from aborted foetuses
To date, there are two human diploid cell lines which were originally prepared from tissues of aborted foetuses (in 1964 and 1970) and are used for the preparation of vaccines based on live attenuated virus: the first one is the WI-38 line (Winstar Institute 38), with human diploid lung fibroblasts, coming from a female foetus that was aborted because the family felt they had too many children (G. Sven et al., 1969). It was prepared and developed by Leonard Hayflick in 1964 (L. Hayflick, 1965; G. Sven et al., 1969) 3Hayflick, The LimitedIn Vitro Lifetime of Human Diploid Cell Strains, Experimental Cell Research, March 1965, vol.37, no. 3, pp. 614-636. G. Sven, S. Plotkin, K. McCarthy, Gamma Globulin Prophylaxis; Inactivated Rubella Virus; Production and Biological Control of Live Attenuated Rubella Virus Vaccines, American journal of Diseases of Children, August 1969, vol. 118, no. 2, pp.372-381. and bears the ATCC number CCL-75. WI-38 has been used for the preparation of the historical vaccine RA 27/3 against rubella (S.A. Plotkin et al, 1965) 4A. Plotkin, D. Cornfeld, Th.H. Ingalls, Studies of Immunization With Living Rubella Virus, Trials in Children With a Strain coming from an Aborted Fetus, American Journal of Diseases in children, October 1965, vol. 110, no. 4, pp.381-389.. The second human cell line is MRC-5 (Medical Research Council 5) (human, lung, embryonic) (ATCC number CCL-171), with human lung fibroblasts coming from a 14 week male foetus aborted for “psychiatric reasons” from a 27 year old woman in the UK. MRC-5 was prepared and developed by J.P. Jacobs in 1966 (J.P. Jacobs et al, 1970) 5P. Jacobs, C.M. Jones, J.P. Bailie, Characteristics of a Human Diploid Cell Designated MRC-5, Nature, 11th July 1970, vol.277, pp.168-170. Other human cell lines have been developed for pharmaceutical needs, but are not involved in the vaccines actually available 6Two other human cell lines, that are permanent, HEK 293 aborted fetal cell line, from primary human embryonic kidney cells transformed by sheared adenovirus type 5 (the fetal kidney material was obtained from an aborted fetus, in 1972 probably), and PER.C6, a fetal cell line created using retinal tissue from an 18 week gestation aborted baby, have been developed for the pharmaceutical manufacturing of adenovirus vectors (for gene therapy). They have not been involved in the making of any of the attenuated live viruses vaccines presently in use because of their capacity to develop tumorigenic cells in the recipient. However some vaccines, still at the developmental stage, against Ebola virus (Crucell,NV and the Vaccine Research Center of the National Institutes of Health’s Allergy and Infectious Diseases, NIAID), HIV (Merck), influenza (Medlmmune, Sanofi pasteur), Japanese encephalitis (Crucell N.V. and Rhein Biotech N.V.) are prepared using PER.C6® cell line (Crucell N.V., Leiden, The Netherlands)..
The vaccines that are incriminated today as using human cell lines from aborted foetuses, WI-38 and MRC-5, are the following: 7Against these various infectious diseases, there are some alternative vaccines that are prepared using animals’ cells or tissues, and are therefore ethically acceptable. Their availability depends on the country in question. Concerning the particular case of the United States, there are no options for the time being in that country for the vaccination against rubella, chickenpox and hepatitis A, other than the vaccines proposed by Merck, prepared using the human cell lines WI-38 and MRC-5. There is a vaccine against smallpox prepared with the Vero cell line (derived from the kidney of an African green monkey), ACAM2000 (Acambis-Baxter) ( a second-generation smallpox vaccine, stockpiled, not approved in the US), which offers, therefore, an alternative to the Acambis 1000. There are alternative vaccines against mumps (Mumpsvax, Merck, measles (Attenuvax, Merck), rabies (RabAvert, Chiron therapeutics), prepared from chicken embryos. (However serious allergies have occurred with such vaccines), poliomyelitis (IPOL, Aventis-Pasteur, prepared with monkey kidney cells) and smallpox (a third-generation smallpox vaccine MVA, Modified Vaccinia Ankara, Acambis-Baxter). In Europe and in Japan, there are other vaccines available against rubella and hepatitis A, produced using non-human cell lines. The Kitasato Institute produce four vaccines against rubella, called Takahashi, TO-336 and Matuba, prepared with cells from rabbit kidney, and one (Matuura) prepared with cells from a quail embryo. The Chemo-sero-therapeutic Research Institute Kaketsuken produce one another vaccine against hepatitis A, called Ainmugen, prepared with cells from monkey kidney. The only remaining problem is with the vaccine Varivax® against chicken pox, for which there is no alternative.
A) Live vaccines against rubella 8The vaccine against rubella using the strain Wistar RA27/3 of live attenuated rubella virus, adapted and propagated in WI-38 human diploid lung fibroblasts is at the centre of present controversy regarding the morality of the use of vaccines prepared with the help of human cell lines coming from aborted foetuses.:
- the monovalent vaccines against rubella Meruvax®!! (Merck) (U.S.), Rudivax® (Sanofi Pasteur, Fr.), and Ervevax® (RA 27/3) (GlaxoSmithKline, Belgium);
- the combined vaccine MR against rubella and measles, commercialized with the name of M-R-VAX® (Merck, US) and Rudi-Rouvax® (AVP, France);
- the combined vaccine against rubella and mumps marketed under the name of Biavax®!! (Merck, U.S.),
- the combined vaccine MMR (measles, mumps, rubella) against rubella, mumps and measles, marketed under the name of M-M-R® II (Merck, US), R.O.R.®, Trimovax® (Sanofi Pasteur, Fr.), and Priorix® (GlaxoSmithKline UK).
B) Other vaccines, also prepared using human cell lines from aborted foetuses:
- two vaccines against hepatitis A, one produced by Merck (VAQTA), the other one produced by GlaxoSmithKline (HAVRIX), both of them being prepared using MRC-5;
- one vaccine against chicken pox, Varivax®, produced by Merck using WI-38 and MRC-5;
- one vaccine against poliomyelitis, the inactivated polio virus vaccine Poliovax® (Aventis-Pasteur, Fr.) using MRC-5;
- one vaccine against rabies, Imovax®, produced by Aventis Pasteur, harvested from infected human diploid cells, MRC-5 strain;
- one vaccine against smallpox, AC AM 1000, prepared by Acambis using MRC-5, still on trial.