Publications worth mentioning
Anti-fertility vaccines
Hundreds of publications over the past decades document the quest to create anti-fertility vaccines. Repeated administration of the vaccine causes the surest fertility block.
Proteins of the human body required to create or maintain a pregnancy are paired with immunogenic epitopes that the immune system reacts strongly against. These immunogenic epitopes are found in the Spike, along with 41 different human fertility epitopes (see Dotan et al. 2021, below).
This method of ‘birth control’ means that every time a woman gets pregnant, her body kills her own child. What would the off-button for this be – total eradication of her immune system? This also means that fertility treatments such as IVF will not work because any implanted embryo will be killed.
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-Despite cross-reactivity to other tissues:
1990: Relevance of immuno-contraceptive vaccines for population control. 1. Hormonal immunocontraception
Gupta SK and Koothan PT, PMID: 2126920
“Human chorionic gonadotropin--subunit beta (beta-hCG) has been so far most extensively studied antigen for immuno-contraceptive properties. Studies of vaccination of non-human primates has been so far controversially reported since some antisera obtained from baboons immunized with beta-hCG had shown cross-reactivity to other tissues. Despite these problems and concerns about the complete safety of this first generation vaccine, a decision has been made to proceed with a limited clinical trial with this vaccine. …
… The human reproductive process entails numerous possible sites for immunological intervention aimed at controlling fertility. Currently under investigation are a vaccine based on gonadotropin releasing hormone (GnRH) interception, regulation of male fertility by immunointerception of follicle-stimulating hormone (FSH), vaccines based on the neutralization of human chorionic gonadotropin (hCG), and anti-hCG immunization. In Phase I clinical trials, … long-term infertility has been achieved through active immunization against the [GnRH] decapeptide…”
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Abnormal menstrual cycles and destruction of pregnancies:
2005: Identification of a heterodimer-specific epitope present in human chorionic gonadotrophin (hCG) using a monoclonal antibody that can distinguish between hCG and human LH
(Gadkari et al. doi: 10.1677/jme.1.01683)
"Human chorionic gonadotrophin (hCG) is secreted during early pregnancy and is required for implantation and maintenance of the pregnancy. Active or passive immunoneutralization of hCG results in termination of pregnancy and this forms the basis of the hCG-based female contraceptive vaccine. However, the beta subunit of hCG possesses 85% sequence homology with the first 114 amino acids of the beta subunit of pituitary human LH (hLH), which is required for ovulation and maintenance of the corpus luteum function during the menstrual cycle. Immunization against hCG or its beta subunit leads to generation of antibodies that can neutralize hLH due to many shared epitopes and hence may cause abnormal menstrual cycles."
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Linking reproductive proteins (hCG) with immunogenic epitopes:
2006: (Xu WX, He YP, Qiu DY, Liao MC, Hong AZ, Ji ZN, Gu SH, Chen JZ, Xie Y. PMID: 17117551)
“Two bio-synthesizing chimeric peptide (CP) immunogens named CP1 and CP10 have been designed, which consist of three linear B cell epitopes (BCE) of human chorionic gonadotropin beta subunit (beta-hCG) and six foreign T cell epitopes including two "promiscuous" TCEs from hepatitis B surface antigen and tetanus toxoid. Two artificial genes encoding CP1 and its derivative CP10 were synthesized… The construction and expression of beta-hCG CP1 and CP10 will provide new immunogens for developing an ideal and superior hCG birth control and/or tumor therapeutic vaccine.”
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All you need is an epitope – a short sequence of the human target protein
2015: Epitope-Specific Anti-hCG Vaccines on a Virus Like Particle Platform
Caldeira J, Bustos J, Peabody J, Chackerian B, Peabody DS.PLoS One. 2015 Oct 30;10(10):e0141407. doi: 10.1371/journal.pone.0141407
The possibility of a contraceptive vaccine targeting human chorionic gonadotropin has long been recognized, but never fully realized. Here we describe an epitope-specific approach based on immunogenic display of hCG-derived peptides on virus-like particles of RNA bacteriophage. A number of recombinant VLPs were constructed, each displaying a different hCG-derived peptide. … Immunization of mice with some VLPs yielded antisera that bound the hormone and neutralized hCG biological activity.
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Goal: amplified immune response
2008: (Li HP, He XJ, Tang CL, Yao XY, Li DJ. doi: 10.1016/j.jri.2008.03.004)
“Contraceptive vaccines based on hCGbeta have not met clinical application because of poor immunogenicity...
… the fusion of hC3d3 to hCGbeta, as a means of harnessing the adjuvant potential of the innate immune system, may contribute to a more efficient humoral immune response, and might provide a potential application of protein vaccine strategies in humans in the future…
…To date, a separate heterospecies vaccine consisting of ovine α-chain noncovalently associated with hCG β-chain conjugated to either tetanus toxoid (TT) or diphtheria toxoid (DT), is the only antifertility vaccine to have completed phase II clinical trials to establish efficacy in humans (Talwar et al., 1994, Talwar, 1999). The heterospecies dimer was successful in preventing pregnancy in moderate to high responders to the vaccine, with only one pregnancy recorded out of 1224 cycles in those immunized females who developed a level of circulating neutralizing antibody >50 ng/ml. However, although all women in the trial produced hCG-reactive antibodies in response to the vaccination, 20% of the 148 females given the initial three primary injections were low responders and failed to develop protective levels of the antibody. The technology underpinning hCGβ vaccine development requires innovations such as the use of cytokines or novel adjuvants to induce selectively specific classes of the immune response.
...hCG, a hormone that indicates the presence of the embryo, is considered essential for both establishment and maintenance of pregnancy. In principle, induction of immunity against hCG should lead to a sequence of normal, or slightly extended, menstrual cycles during which pregnancy would be terminated around the blastocyst stage of embryo. …”
DNA vectors or Viral vectors to achieve gene expression in host cells:
“… To enhance the immunogenicity of the hCG contraceptive vaccine, we have chosen C3d3 as a molecular adjuvant of hCG DNA vaccine based on pcDNA3 (Li et al., 2003), phCMV1 (Wang et al., 2004) and pCMV4 (Wang et al., 2006) vector ... In order to apply the hCG contraceptive vaccine in humans, in the present study, we have conjugated a new hCG-hC3d3 fusion vaccine containing the molecular adjuvant based on the pCI vector.”
...C3d, a split product of [complement factor] C3, interacts with its receptor (CR2 or CD21) on B cells and follicular dendritic cells (FDCs) and is crucial for induction and maintenance of a normal humoral immune response (Carroll, 2000). It has been shown that DNA immunization with plasmids encoding influenza virus hemagglutinin (Ross et al., 2000), measles virus hemagglutinin (Green et al., 2002) or HIV envelope protein gp120 (Green et al., 2003) covalently linked to three C3d domains elicited a much higher level of antigen-specific antibodies of enhanced affinity than these antigens alone...
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Unknown unknowns:
2006: Complement 3d: from molecular adjuvant to target of immune escape mechanisms.
(Bergmann-Leitner et al. doi: 10.1016/j.clim.2006.07.001)
“C3d is a fragment of the complement factor C3 and is generated in the course of complement activation. When bound to antigen in single or multiple copies, the B cell receptor and complement receptor 2 become co-crosslinked resulting in decreased or increased B cell responses depending on the valence of the antigen-C3d construct. When antigen-C3d constructs are used for the purpose of generating a protective immune response (vaccines), they may either enhance the expected response or suppress it depending on the nature of the antigen. Various pathogens use C3d to evade the immune system by inhibiting complement activation, invading and homing in host cells or masking immunogenic areas of pathogen proteins. Therefore, future vaccination strategies for infectious diseases and cancer employing C3d as a molecular adjuvant need to be carefully evaluated before choosing a target antigen in order to take advantage of the adjuvant effect of the complement component while avoiding potential vaccine complications associated with immune escape mechanisms.”
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Boosters + amplified immunogenicity:
2011: Development of a highly immunogenic recombinant candidate vaccine against human chorionic gonadotropin.
(Purswani and Talwar, doi: 10.1016/j.vaccine.2010.11.069)
Human chorionic gonadotropin (hCG) is synthesized soon after fertilization and is essential for embryonic implantation. A vaccine targeting hCG would be an ideal choice for immuno-contraception … Trials established the threshold levels of bio-neutralizing anti-hCG antibody titers required to prevent pregnancy; however, these titers (>50 ng/ml) were achieved in only 80% of immunized women. In this communication, we report a novel recombinant anti-hCG vaccine which demonstrates improved immunogenicity. hCG was genetically fused … [to] E. coli heatlabile enterotoxin. The recombinant fusion protein (hCG-LTB) … along with Mycobacterium indicus pranii (MIP) as an immuno-modulator, evoked a very high anti-hCG immune response in 100% of immunized BALB/c mice. …
A schedule of 3 intramuscular fortnightly injections was employed for primary immunization. The recombinant vaccine adsorbed on Alhydrogel generated a feeble antibody response [21]. The antibodies were detectable to begin with, on day 45 reaching maximum titers of 458 ng/ml (geometric mean) on day 75. Though all mice on 75th day had titers above 50 ng/ml, the antibodies declined within 15 days thereafter. The overall response was moderate and short-lived necessitating the use of an adjuvant.
MIP was developed as an immunotherapeutic adjunct against leprosy [22]... MIP… was given intra-muscularly on the other flank of mice receiving hCG-LTB ... The combination was remarkably better for generating anti-hCG response. Antibodies were measurable within 1 week of completion of primary immunization. All mice without exception produced antibodies of titers ranging between 405 ng/ml and 5130 ng/ml … on day 37. A booster on day 127 led to resurgence of the antibody titers in every mouse to as high as 3600–17,830 ng/ml …on day 165. The titers declined gradually with time, reaching a geometric mean of 1190 ng/ml on day 240 indicating the waning of the response with time in the absence of booster immunisation... Every mouse … made bioneutralizing antibodies of titers well above 50 ng/ml, the protective threshold of pregnancy in women.”
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DNA, RNA:
2015: Priming with DNA Enhances Considerably the Immunogenicity of hCG β-LTB Vaccine
Nand KN, Gupta JC, Panda AK, Jain SK, Talwar GP. Am J Reprod Immunol. 2015 Oct;74(4):302-8. doi: 10.1111/aji.12388.
Problem: Necessity to elicit antibody response above the protective threshold titres by sexually active women immunized to prevent pregnancy.
Method of study: Recombinant hCGβ-LTB vaccine expressed as both DNA and protein. Balb C mice employed for testing immunogenicity.
Results: Necessity to give three primary injections of the vaccine to elicit proper antibody response. Immunization twice with DNA form of the vaccine at fortnightly interval followed by the protein elicits a distinctly higher antibody response than proteinic vaccine alone. Antibodies generated are bio-effective against hCG.
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Classic antigen + human reproductive protein = infertility
By now we see the basic recipe of how to induce autoimmune attack against the body’s reproductive tissues and hormones, which has been developed and tested for decades. Simply combine a primordial antigen that the body is sure to recognize (e.g. bacteria, virus, parasite) with a protein necessary for reproduction. What do we find in the Spike?
This article was pointed out to me by Substack user Castigator:
Antigenic sites in SARS-CoV-2 spike RBD show molecular similarity with pathogenic antigenic determinants and harbors peptides for vaccine development.
Dakal TC. Immunobiology. 2021 Sep;226(5):152091. DOI: 10.1016/j.imbio.2021.152091
"In current study, we performed an integrative approach to predict antigenic sites in SARS-CoV-2 spike receptor binding domain and found nine potential antigenic sites. The predicted antigenic sites were then assessed for possible molecular similarity with other known antigens in different organisms. Out of nine sites, seven sites showed molecular similarity with 54 antigenic determinants found in twelve pathogenic bacterial species (Mycobacterium tuberculosis, Mycobacterium leprae, Bacillus anthracis, Borrelia burgdorferi, Clostridium perfringens, Clostridium tetani, Helicobacter Pylori, Listeria monocytogenes, Staphylococcus aureus, Streptococcus pyogenes, Vibrio cholera and Yersinia pestis), two malarial parasites (Plasmodium falciparum and Plasmodium knowlesi) and influenza virus A."
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The following articles about immunogenic epitopes appearing in the Spike were brought to attention in an excellent piece by DoorlessCarp (link below).
2021: From Anti-Severe Acute Respiratory Syndrome Coronavirus 2 Immune Response to Cancer Onset via Molecular Mimicry and Cross-Reactivity
(Kanduc D. doi: 10.1055/s-0041-1735590).
[Table 3] Bordetella pertussis, Clostridium tetani, Cornyebacterium diptheriae, Haemophilus influenzae, Neisseria meningitides.
Here, Kanduc discusses the immunogenic epitopes in the context of tumor-suppressor proteins, but reveals in the next article a “Molecular mimicry between SARS-CoV-2 and the female reproductive system.” This demonstrates the classic combination of reproductive protein + immunogenic epitope.
“Potential Immunologic Imprint: The 29 pentapeptides common to SARS-CoV-2 spike gp and tumor-suppressor proteins … are not only present in immunoreactive epitopes … but, in addition, almost all of them (24 out of 29) are also present in microbial organisms such as Bordetella pertussis , C. diphtheriae , C. tetani , H. influenzae , and N. meningitides ( Table 3 ). That is, most of the shared peptides are also present in pathogens that an individual possibly encountered during his life because of infections and/or vaccinal routes.
Such interpathogen peptide commonality introduces the immunologic memory as a factor capable of enhancing the extent of the immune cross-reactive response against the tumor-suppressor proteins. That is, as already described since 1947, (48, 49) the immune system does not induce ex novo primary responses toward a recent infection. Rather, the immune system recalls, amplifies, and intensifies preexisting memory responses toward past infections. In this way, what should have been a primary response to a recent infection is transformed into an anamnestic, secondary, and magnified response to past infections. Simply put, as already discussed in previous reports, (50, 51, 52, 53, 54, 55) the early history of the individual's infections/vaccinations dictates the immune outcomes of any successive infections/vaccinations.
The immunologic imprint phenomenon has its molecular foundations in the massive peptide sharing that characterizes microbial and human proteins (17, 56, 57) and of which Table 3 is an example. The implications are noteworthy. In the case object, following exposure to SARS-CoV-2 by infection or vaccination, the expected primary response to the virus can turn into a secondary response to previously encountered pathogens against which the immune system already reacted and of which has stored an immunologic memory, that is, the microbial organisms reported in Table 3 . However, the previously encountered pathogens are no more present in the human organism, so that the anamnestic immune response triggered by the exposure to SARS-CoV-2 by infection or vaccination ends to divert onto available immune determinants that, in the present case, are the common determinants present in the tumor-suppressor human proteins. Pathologically, one has to consider that usually an anamnestic secondary immune response is characterized by high avidity and high affinity, besides being quantitatively relevant. Therefore, as a final result, exposure to SARS-CoV-2 by infection and/or vaccination can trigger immediate and violent cross-reactive attacks against the proteins that protect the human being from carcinogenesis.”
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Reproductive proteins [below] + immunoreactive epitopes [above]
2021: Molecular mimicry between SARS-CoV-2 and the female reproductive system
Dotan A, Kanduc D, Muller S, Makatsariya A, Shoenfeld Y.doi: 10.1111/aji.13494
“Oogenesis, the process of egg production by the ovary, involves a complex differentiation program leading to the production of functional oocytes. …The question related to SARS-CoV-2 infection and fertility has been evoked for several reasons, including the mechanism of molecular mimicry, which may contribute to female infertility by leading to the generation of deleterious autoantibodies, possibly contributing to the onset of an autoimmune disease in infected patients…
SARS-CoV-2 spike glycoprotein was found to share 41 minimal immune determinants, that is, pentapeptides, with 27 human proteins that relate to oogenesis, uterine receptivity, decidualization, and placentation.”
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The articles by Kanduc (2021) and Dotan et al. (2021) were brought to attention by DoorlessCarp in an excellent piece on epitopes embedded in the spike:
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Articles cited here are for educational or informational purposes only. Please refer to the copyrights of the owners.
Thank you for reading.
Thanks for collating these. I don't believe in coincidence.