Pathophysiology of Vaccine Injury After Coadministration of MMR and Aluminum Containing Vaccines Here I propose that administration of MMR vaccine in combination with aluminum containing vaccines, causes brain damage through a unique interaction between the various ingredients in both vaccines, and the innate complement system of the brain. For this interaction to occur, the Edmonston strain measles virus and insoluble aluminum adjuvant particles must cross the blood brain barrier. Aluminum adjuvant nano particles are phagocytosed by macrophages [1, 2, 3]. Macrophages can cross the blood brain barrier as a result of inflammation from the liver, or activated microglia producing macrophage chemoattractant protein [4]. The brain in an immune privileged site, and therefore generally limits entry of cells and proteins into the CNS. The brain relies heavily on innate immunity, which is expressed throughout the brain, including virtually all components of complement which are locally produced. Furthermore, studies indicate complement activation products are involved in brain development and synapse formation [5]. During development, the formation of mature neural circuits requires the selective elimination of inappropriate synaptic connections. Mice deficient in complement protein C1q or the downstream complement protein C3 exhibit large sustained defects in CNS synapse elimination. These findings support a model in which unwanted synapses are tagged by complement for elimination and suggest that complement-mediated synapse elimination may become aberrantly reactivated in neurodegenerative disease [6]. The complement pathway is strongly activated by aluminum hydroxide adjuvants, more specifically resulting in deposition of C3 cleavage products and membrane attack complexes [7]. Under normal conditions it is important that C3 regulatory factors inhibit the C3 deposition to prevent development of membrane attack complexes, and ultimately lysis of host cells. During hyper-activation resulting from aluminum exposure, this regulatory process becomes ever more critical. It is established that measles virus can cross the blood brain barrier via a transcellular and or by “Trojan horse” pathway [8]. Inside the brain, measles virus (Edmonston strain) interacts with and downregulates the major measles virus receptor CD46 (MCP). This occurs from surface contact between the host cells can virus, or infected cells. As a result of CD46 downregulation, an increased susceptibility of uninfected cells for complement-mediated lysis was observed, suggesting vaccination may also lead to complement mediated cell lysis [9]. This can be explained by looking at the role of CD46 as a complement regulatory protein that protects host cells from injury by complement by inactivating C3b deposited onto host cells [10]. Excessive and uncontrolled activation of the complement has been implicated in the host of autoimmune diseases [11]. Aluminum adjuvants and measles virus may therefore create a synergistic effect that can potentially damage tissues of the brain through an inverse relationship between insoluble aluminum and the Edmonston strain measles virus. To clarify this synergistic relationship, we must understand that aluminum strongly induces C3 activation while simultaneously measles virus strongly inhibits the regulatory protective mechanism CD46, thereby promoting host cell mediated lysis at a greatly accelerated rate via C3b deposition and ultimately the terminal complement pathway.
References: 1. Rimaniol et al., 2004: Aluminum Al uminum hydroxide adjuvant induces macrophage differentiation differentiati on towards a specialized antigen-presenting cell type 2. Eisenbarth et al., 2008: Crucial role for the Nalp3 inflammasome in the immunostimulatory immunostimul atory properties of aluminum adjuvants 3. Gherardi et al., 2001: Macrophagic myofasciitis myofasciiti s lesions assess long-term persistence of vaccine-derived aluminum hydroxide in muscle 4. D’Mello et al., 2009: Cerebral Microglia Recruit Monocytes into the Brain in Response to Tumor Necrosis Factor Signaling during Peripheral Organ Inflammation 5.
Veerhuis R et al., 2011: Complement in the brain
6. Stevens B et al., 2007: The classical complement cascade mediates CNS synapse elimination. 7. Güven E et al., 2013: Aluminum hydroxide adjuvant differentially differential ly activates the three complement pathways with major involvement of the alternative pathway. 8.
Acta Virol et al., 2017: How viruses infiltrate the central nervous system.
9. J Virol et al., 1996: Receptor (CD46) modulation and complement-mediated complement-medi ated lysis of uninfected cells after contact with measles virus-infected cells. 10. Hum Genomics et al., 2015: Complement regulator CD46: genetic variants and disease associations 11. Clin Chim Acta et al., 2017: Complement in autoimmune diseases
