vaccination support

Pathophysiology

In general we develop immunity to disease in two ways:

Primary Infection:  Pathogenic infectious agents stimulating a host immune system response (humoral and cell mediated immunity) that mitigates pathogenic infection including antibody production that promotes recovery and subsequent acquired immunity.

Vaccination: Exposes the body to antigens that mimic disease causing pathogens, stimulating adaptive immunity and memory of the antigen without causing the disease.  The process of acquiring vaccine immunity is referred to as immunisation.

• Immunological mechanisms of vaccinations (Figure 1) are acquired as follows:
  • Once administered, antigen-presenting cells (APCs) capture the vaccine antigen, displaying it on the APC surface and subsequently stimulating T helper (Th) cell activation, which identify the antigen as foreign.[3]
  • Naïve B cells are activated, which recognise the vaccine antigen displayed on APCs, prompting B cell division and synthesis of active B cells that are specific to the vaccine antigen.[4]
  • Upon receiving signals from activated Th cells, B cells mature into plasma B cells that produce and secrete antibodies specific to the vaccine antigen.[5]
  • Antibodies bind and attach to the target vaccine antigen (akin to a lock and key mechanism). This prevents the antigen from entering a cell, while also marking it for destruction.[6]
  • Killer T cell response is generated. If the vaccine contains attenuated viruses, killer T cells identify and destroy infected cells.[7]
  • Memory B cells retain memory of the vaccine antigen for future recognition, which primes the immune system to elicit a faster and stronger response in the event of future pathogenic exposure.[8]
• Substantial variation exists between individual immunity in response to vaccination. For instance, the antibody responses to Haemophilus influenzae type b (Hib) vaccination vary >40-fold, while hepatitis B vaccination varies >100-fold.[9] Factors that influence humoral and cellular vaccine responses include[10]:
  • Intrinsic host factors: Age, sex, genetics, and comorbidities.
  • Perinatal factors: Gestational age, birth weight and feeding method.
  • Extrinsic factors: Microbiota and infections.
  • Behavioural factors: Smoking, chronic psychological stress and sleep.
  • Nutritional factors: Body mass index (BMI) and micronutrient status.
• Five main types of vaccines available include[11]:
  • Live attenuated vaccines (e.g. measles, mumps, and rubella [MMR] and varicella [chickenpox]): Contain a version of the living virus or bacteria that have been engineered to have substantially reduced virulence (weakened), so as not cause serious disease in people with healthy immune systems.[12]
  • Inactivated vaccines (e.g. polio, hepatitis A and rabies): Are comprised of microorganisms that have been rendered non-infectious (killed) by chemical or physical means. Inactivated vaccines often require multiple doses to build up or maintain immunity.[13]
  • Toxoid vaccines (e.g. diphtheria and tetanus toxoids): Prevent diseases caused by bacteria that produce toxins (poisons) in the body. Toxoid vaccines are made from weakened toxic compounds rather than the microorganism.[14]
  • Subunit vaccines (e.g. pertussis [whooping cough], hepatitis B, human papillomavirus {HPV}): Contain a fragment of the bacteria or virus (the essential antigens) rather that the entire germ, making side effects to the vaccine less common.[15]
  • Conjugate vaccines (Hib): Target specific bacteria that contain a polysaccharide outer coating, which make it increasingly difficult for the immune system to recognise and respond to the antigen. Conjugate vaccines link polysaccharides to the antigen, enhancing immune system recognition.[16]
  • Nucleic acid-based vaccines (e.g. Pfizer-BioNTech Covid-19): Genetic vaccines consisting of deoxyribonucleic acid (DNA) or messenger ribonucleic acid (mRNA) sequences that translate proteins, which induce an immune response and code for a disease-specific antigen.[17],[18] Nucleic acid-based vaccines do not require the growth of highly pathogenic organisms at a large scale, therefore reducing risk of contamination with live infectious reagents and release of dangerous pathogens, as well as decreasing manufacturing time.[19]
  • Viral vector vaccines (e.g. Oxford-Astra Zeneca Covid-19 vaccine): Use a modified, low-pathogenic virus, such as adenoviruses, parvoviruses or paramyxoviruses, to function as a vector that shuttles one or more different pathogenic antigens into host cells, inducing an immune response against the target pathogen.[20]

Treatment RecommendationsCore RecommendationsHigh Bioavailability Zinc with Vitamin C
Zinc and vitamin C to support the development, function and mediation of immune cells required to strengthen the immune response and enhance vaccine efficacy.
Mechanism of Action/Clinical Research:

• Zinc is involved in several aspects of immunological function, including the development, function and mediation of immune cells such as neutrophils, monocytes and natural killer (NK) cells, as well as the development of acquired immunity and T lymphocyte function[62]; which are important processes for infection prevention and maintaining vaccine immunity.[63]
  • A prospective longitudinal study involving 208 children aged between 7 months to 15 months found a positive association between serum zinc levels and tetanus vaccine titres, indicating that zinc status may enhance immunological memory.[64]
• Vitamin C supplementation has been shown to reduce the duration and severity of infections[65] and is increasingly efficacious when combined with zinc, with deficiencies of vitamin C and zinc both severely compromising immune responses.[66]
• Vitamin C stimulates white blood cell production and function, enhances NK cell activity and chemotaxis, supports clearance of spent neutrophils from sites of infection, increases serum levels of antibodies, and augments lymphocyte differentiation and proliferation;[67] facilitating innate and adaptive immune responses necessary for acquiring immunity.
  • Studies have shown that experimentally induced vitamin C deficiency leads to impaired cellular and humoral immune response.[68]
  • Vitamin C supplementation of 200 mg/d administered for one to three months was shown to increase IgG and IgM serum levels and improve humoral immune response in the ageing population.[69]

Vitamin D3
Vitamin D to modulate innate and adaptive immunity, necessary to illicit a strong immune response to acquire vaccine immunity and increase host resistance to infection.
Mechanism of Action/Clinical Research:

• It is well known that vitamin D plays an important role in regulating immune function, with deficiency impacting the activity of T regulatory (Treg) cells[70],[71] and Th cells[72], as well as the production of antibodies and regulation of dendritic cell function.[73]
• Vitamin D enhances the adaptive immune response by increasing the differentiation of monocytes to macrophages and stimulating white blood cell proliferation, essential to the neutralisation of viral infections.[74]
• With receptors expressed on a wide variety of cell types, vitamin D is involved in the modulation of activated T and B lymphocytes, necessary for acquired immunity.[75]
  • A retrospective study involving 200 patients with chronic kidney disease who had undergone hepatitis B vaccination found that patients with vitamin D deficiency <10 ng/mL (equivalent to 25 nmol/L) demonstrated lower seroconversion rates and antibody formation compared to patients with higher vitamin D status.[76]

Select a probiotic formula that corresponds to the patient’s age.
For adults and children over 12 years:
​Mechanism of Action/Clinical Research:

• Probiotics induce cellular immunity in phagocytic and NK cells, and promote IgA secretion into saliva to enhance vaccine effects. Additionally, probiotic metabolites, such as short-chain fatty acids (SCFAs), and the peptidoglycan components of probiotics, exert benefits on the host gut epithelium and microbiota by modulating the immune function.[77]
• Lactobacillus paracasei administration has been found to increase the length of time a vaccine is effective.[78]
  • A meta-analysis of randomised control trials found that probiotic interventions, including Lactobacillus paracasei, administered for 2 to 28 weeks improved seroconversion and seroprotection rates to influenza vaccines (including H1N1, H3N2 and B strains).[79]
• Studies have demonstrated Lactobacillus plantarum (HEAL9), Lactobacillus paracasei (8700:2) and Lactobacillus rhamnosus (LGG®) all have the capacity to induce IL-10, a key anti-inflammatory and immunoregulatory cytokine, which is expressed by Tregs and Th2 cells.[80]
• LGG® has been shown to protect against viral infection, including the common cold and influenza, by stimulating respiratory NK cell activity, and up-regulating antiviral interferon gamma (IFN-γ).[81],[82]
  • A clinical trial involving 898 participants who were administered 500 million colony forming units (CFU)/d each of HEAL 9 and 8700:2 for 12 weeks revealed a 30% reduction in the incidence of recurring colds and an 18% decline in analgesic use compared to placebo.[83]
  • A randomised, parallel, double-blind, placebo-controlled study involving 272 subjects supplemented with either 500 million CFU each of HEAL9 and 8700:2 or placebo for 12 weeks demonstrated a 28% reduction in the duration of the common cold and a reduction in total symptom scores by 24%.[84]
• L. plantarum (HEAL9) and L. paracasei (8700:2) have been shown to stimulate the innate immune response.[85]

​References
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