C.98-GARDASIL ANTI-PAPILLOMAVIRUS VACCINE: MOLECULAR MIMICRY OF HPV L1 WITH GONADOLIBERIN GNRH EXPLAINING PRECOCIOUS MENOPAUSE AND STERILITY

After Gardasil vaccination, a 16 years old Australian (Little DT, 2012) and a 18 years old French Jennifer Sellier (Carrère d’Encausse M, 2015) developped a premature menopause and sterility. Four more Australians were further reported (Little DT, 2014). In September 2015, the Vaccine Adverse Event Reporting System (VAERS) reported 95 irreversible cases among 104 early menopauses. This number did not reflect the reality, as only <1% to 10% are declared, owing to the fact that menopause is unknown from the general practionner as a Gardasil complication (NVIC). Therefore, in reality, there is 10 000 cases of sterility, a number which will grow continuously with time. The September 2015 French pharmacovigilance ANSM/CNAMTS report followed 14 auto-immune diseases, but did not include menopause/sterility among them, despite the fact that infertility can be induced by an immune mechanism, for example by woman antibodies against husband sperm, and fertility recovered by deletion of these antibodies. A FDA cohort began in Sweden with 3000 patients, this number fell to 1700 after 6 years, to 500 after 8 years, then the study was never terminated and simply burried. Gardasil was licensed in the market without any released data on the ovaries of the Sprague-Dawley female rats. Furthermore, Sprague-Dawley rats are prone to cancer, and are not the species of choice in the case of auto-imune disease. The data on male rats were stopped prematurely at the second injection. Tween 80 (polysorbate 80) containing ethylene glycol can provoke severe ovary deformities, degenerative follicles, sterility (Gajdova M, 1992) and anaphylactic shock. Some countries such as Japan, Denmark or Western European countries have yet a worrying decline of fertility. We investigated the auto-immune mechanism of sterility induced by Gardasil.

METHODS We compared the amino acid (AA) sequences of the Gardasil 9 vaccine HPV L1 and Gonadotropin Releasing Hormone GnRH, mumps virus (ovaritis, orchitis and sterility if during post-puberty). Mycoplasma and Enteroviruses [Coxsackie A6 (Foot Mouth Hand Disease or FMHD), Echovirus, Enterovirus E or Bovine Enterovirus (BEV)] were included, because Coxsackievirus A6 orchitis was reported in Finland; and in bull, orchitis, loss of libido, testicular degeneration, aspermatogenesis and sterility occurred after a BEV-1 infection (Weldon SL,1979). BEV has a large spectra and can infect humans.

RESULTS There is a molecular mimicry EHWS between HPV-57, -2, -27 L1 and the catfish, dogfish GnRH active site, Mycoplasma Salivarium (WP_024544007), extending to 6 AAs  EHWSKG and pEHWSHG (p=pyrrolidone).

We found a molecular mimicry between HPV-16, -18, -11, -6 L1 163-EHW and the GnRH active site  24-pEHW-26, prolonged upstream to 2 Cys 153-CMVGC-157 and 17-CVVGC-21.  GnRH (homo, teleost) 31-SPGGKRNAE-39 matches with HPV (-3, -34 chimera) 198-TPCGKQNAgE-207 (Span=28 AA).

Hypogonadotropic Hypogonadism 12 mutation R → C                              C

GnRH                            CV VGC SSpEHWS HGLSPGGKRNA E

PVH L1                         CMVGCapplgEHWGKGLSPCGKQNAgE

Mumps virus F                                   EQWS YPAKNC

Coxsakievirus A6        ALVFP         (Q,H)WINLRTNNCA

Enterovirus E VP2            LIYP          (Q,H)WINLRTNNS A

Mycoplasma Salivarium                  80-EHWSKG

Glutamine Q and Histidine H are cross-reactive, owing to their chemical similarities. A length of only 3 AAs is enough for a hypothalamic hormonal activity (i.e. TSH Releasing Factor pGln-His-Pro, Melanostatin Pro-Leu-Gly). The mutation R31C of GnRH 24-pEHWSYGLRPG-33 induces a Hypogonadotropic Hypogonadism 12 (HH12). C31 almost aligned with C171 of L1 163-EHWGKGKQC-171 and C324 of mumps virus F (Fusion) protein 315-EQWSYPAKNC-324. The most worrying is the discovery that Gardasil 9 contains 9 times the EHW motif, highly conserved in 71/75 (94,7%) studied HPV types.

CONCLUSION

Gardasil L1 mimics the GnRH active site pEHWxxG and is homologous to mumps virus F, Coxsackie A6 (FMHD) and Mycoplasma, all three responsible of sterility. This is coherent with an auto-immune disease directed against GnRH which is destroyed by anti-GnRH auto-antibodies cross-reactive with vaccine L1, in particular L1 of HPV-6 and -11, absent in Cervarix. Japan has suspended Gardasil in June 2013, India in 2010. As for mumps virus, pubescent adults are susceptible to have complications conducting to a definitve sterility, particularly in the feminine sex very prone to auto-immunity (they have a more reactive HLA system). One third of young women take oral contraceptives that can mask this complication during all the time they take the pill, so infertility may only develop when stopping contraception, about 15 years later, in the 2030s. The 3 intra-muscular injections provoke a powerful, durable and aggravating anamnestic response [induced by Aluminium-DNA complex (Lee SH, 2012)], which is 10 times more powerful than the natural infection. The Gardasil 4 HPV types possess the pEHWxxG motif, and more dramatically the Gardasil 9 have it 9 times. The obligatory Measles Mumps Rubella vaccine may enhance the auto-antibodies. Undetected enterovirus E infection on a background of selenium deficiency may aggravate the situation. Mycoplasma Salivarium contains also a GnRH epitope.

Plasmapheresis may be a possible solution to delete anti-GnRH auto-antibodies. Selenium levels must be determined and corrected. Selenium has an antiviral activity against enteroviruses.

BIBLIOGRAPHY

ANSM/CNAM report Sept 2015

Carrère d’Encausse M. Les médicaments sont-ils parfois dangereux pour notre santé? French TV 5, 10.2.2015.

Gajdova M. Food Chem Toxicol 1992, 31:180-90.

Lee SH. Detection of human papillomavirus L1 gene DNA fragments in postmortem blood and spleen after Gardasil® vaccination—A case report. Adv Biosc Biotech, 2012, 3: 1214-24

Little DT. Premature ovarian failure 3 years after menarche in a 16-year-old girl following human papilloma-virus vaccination. BMJ Case Rep 2012. 10.1136/bcr-2012-006879.

Little DT. Adolescent Premature Ovarian Insufficiency Following Human Papillomavirus Vaccination. A Case Series Seen in General Practice. J Investig Med High Impact Case Rep 2014, 2: 2324709614556129.

Little DT. Human papillomavirus vaccine and the ovary: the need for research. Paper presented at: Proceedings of the 18th World Congress on Controversies in Obstetrics, Gynecology and Infertility; October 24-27, 2013; Vienna, Austria.

NVIC.Org

SANEVAX

Weldon SL. Isolation of picornavirus from feces and semen from an infertile bull. J Am Vet Med Assoc 1979, 174:168-9.

Aknowlegments to Caprani A., President of Positifs Association, Positifs.org for financial support.