Herd Immunity & Antibodies

 

Herd immunity is a theory put forth describing immunity through vaccinating a significant portion of a population (called “the herd”). Since not everyone who receives a vaccine develops an antibody, it is presumed that if most are vaccinated, the “herd effect” will protect those without an antibody from getting sick. Herd immunity theory proposes that contagious diseases are transmitted from individual to individual and that the transmission can be stopped when large numbers of a population are immune or less susceptible to the disease.

Epidemic Theory: Herd Immunity Encyclopedia of Public Health

W135 strain of the disease The emergence of Neisseria meningitidis W135 “It is probable that production capacity of vaccines targeting the serogroup W135 will remain insufficient for the next epidemic seasons. WHO is working with manufacturers to make available an effective vaccine against the circulating strains, including N.meningitidis W135 at an affordable price for countries most at risk. In addition, the current polysaccharide vaccine has some drawbacks for vaccination campaigns in sub-Saharan Africa: it does not provide long-lasting protection, hence the need for repeated vaccination of at least 80% of the population each time an epidemic occurs; logistic demands and costs are very high; the vaccine has no effect on colonization or transmission of the organism within populations, so travelers returning from an epidemic zone can transmit the infection to close contacts.”

SLIDES AND NOTES History and Epidemiology of Global Smallpox Eradication (pdf)

Self-boosting vaccines and their implications for herd immunity

May 3, 2022 – Transmissible and Transferable Vaccines “Many of these diseases have the potential to spread to humans, or have already done so. SARS-CoV-2, the virus that causes COVID-19, is only one of the recent diseases caused by zoonotic spillover. Infectious disease experts are aware of many animal populations – such as bats – that can act as reservoirs for zoonotic viruses. Vaccination of individual animals is only one of the many strategies employed to slow the spread of these pathogens.’

September 7, 2015 – Downfall of the current antibody correlates of influenza vaccine response in yearly vaccinated subjects: towards qualitative rather than quantitative assays “Response to seasonal influenza vaccination is currently evaluated by antibody correlates that estimate vaccine seroconversion as well as immune-protection. These correlates rely on the general dogmas surrounding seasonal influenza vaccination, i.e. that vaccine-induced antibodies would exclusively generate immunity to influenza vaccine-strains and that protective immunity would wane before the next season. Here we summarize recently reported data on immunity to seasonal influenza in healthy individuals and re-discuss results on yearly vaccinated pediatric immune compromised patients that together highlight the need for revision of the current correlates of vaccine response to shift from quantitative to qualitative measurements.”

May 26, 2015 Altered antibody response to vaccination in patients with SLE“In a new study of influenza immunization in patients with SLE, Kaur etc al. show that these patients have an enhanced antibody response to nonself antigens when compared with healthy individuals.”

May 21, 2015 Immune overload: Parental attitudes toward combination and single antigen vaccinesCombination vaccines make vaccination more efficient by incorporating the antigens of several different diseases into a single injection, but many parents worry that they may overload the child’s developing immune system and leave him or her susceptible to secondary infections.”

May 14, 2015 Herd immunity and the herd severity effectTheir finding is somewhat counterintuitive: higher vaccination rates that approach herd immunity levels mean that fewer people overall get sick, but those who get sick might have much more severe illnesses than in previous generations.”

February 2, 2015 – The genetic regulation of infant immune responses to vaccination (full text) “This paper reviews the evidence to date that host genes influencing vaccines responses in these older population and identifies a large gap in our understanding of the genetic regulation of responses in early life. Given the high mortality from infection in early life and the challenges of developing vaccines that generate effective immune responses in the context of the developing immune system further research on infant populations is required.”

January 8, 2015 – A sense of immunity: Scientists are detailing the immune system as never before “By the end of this winter, as many as 150 million people in the US may have received this season’s flu vaccine, but not all of them will be protected from catching the flu. In fact, up to 40% of people over the age of 60 won’t even make antibodies in responses to the vaccine.”…”The Stanford researchers are looking for new ways to define immune health and predict successful responses to vaccines. “The only surrogate marker we’ve had for vaccine development has been antibody responses, and antibody responses are not that important for a lot of diseases,” Davis says.”

August 17, 2014 Humoral responses to independent vaccinations are correlated in healthy boosted adults “Vaccination responses are predominantly robust and vaccine specific. However, a small but significant portion of the vaccinated adult population may not have quantitative seroprotective antibody to common vaccine-preventable infections.”

July 15, 2014 –  Sex-based Biology and the Rational Design of Influenza Vaccination Strategies “Females develop higher antibody responses, experience more adverse reactions to influenza vaccines, and show greater vaccine efficacy than males. Despite greater vaccine efficacy in females, both young and older females are often less likely to accept influenza vaccines than their male counterparts. Identification of the biological mechanisms, including the hormones and genes, that underlie differential responses to vaccination is necessary. We propose that vaccines should be matched to an individual’s biological sex, which could involve systematically tailoring diverse types of FDA-approved influenza vaccines separately for males and females.”

July 15, 2014 – Sex Differences in Infectious Diseases–Common but Neglected “Only recently, the biological pathways responsible for these sex-based differences in the manifestations of infectious diseases have been started to be unveiled. These include immunological pathways affected by sex hormones, as well as consequences of differential expression of X-chromosome–encoded genes on immune responses to pathogens. Further research is required to gain a better understanding of the differences in immunity to infections between women and men in order to develop individualized treatment concepts in infectious diseases that take sex-specific host factors into account.”

June 30, 2014 – Challenges in vaccination of neonates, infants and young children “Despite high vaccine compliance, outbreaks of vaccine-preventable infections are occurring worldwide. These data strongly argue for an improved understanding of the immune responses of neonates, infants and young children to vaccine antigens and further study of the exploitable mechanisms to achieve more robust and prolonged immunity with fewer primary and booster vaccinations in the pediatric population.”

May 30, 2014 – Commentary: Potential implications of non-specific effects of childhood vaccines “Emerging evidence suggests that vaccines can positively or negatively affect the resistance to other infectious diseases—the so-called non-specific effects of vaccines or non-specific immunomodulation by vaccines.The bulk of this evidence has been generated from Guinea-Bissau by researchers led by Peter Aaby. The current status of global evidence has been summarized by them in this issue of IJE4 and elsewhere. On this basis, they also suggest a new definition of vaccines:”

May 29, 2014 – Could moderate alcohol intake be recommended to improve vaccine responses? “There is strong evidence that chronic ethanol abuse is associated with increased morbidity and mortality, immunosuppression and increased susceptibility to both bacterial and viral infections. In contrast, moderate alcohol consumption exerts positive effects including decreased mortality, and improved cardiovascular disease and insulin sensitivity. Interestingly, accumulating evidence also supports an immune-boosting effect of moderate alcohol.”

May 23, 2014 – How advances in immunology provide insight into improving vaccine efficacy “Despite the importance of vaccinology, we are still in the early stages of understanding how the best vaccines work and how we can achieve better protective efficacy through improved vaccine design. Most successful vaccines have been developed empirically, but recent advances in immunology are beginning to shed new light on the mechanisms of vaccine-mediated protection and development of long-term immunity. Although natural infection will often elicit lifelong immunity, almost all current vaccines require booster vaccination in order to achieve durable protective humoral immune responses, regardless of whether the vaccine is based on infection with replicating live-attenuated vaccine strains of the specific pathogen or whether they are derived from immunization with inactivated, non-replicating vaccines or subunit vaccines.”

March 3, 2014 – Recommendations for live viral and bacterial vaccines in immunodeficient patients and their close contacts (full text)

  • In 2010, an infant in South Africa received 3 doses of poliovirus vaccine (oral vaccine at birth and inactivated vaccine at 10 and 14 weeks of life) before identification of his diagnosis of SCID.10 At 10 months of life, the child had fever, vomiting, tonic-clonic seizures, and acute flaccid paralysis. Poliovirus 3 was identified in a stool sample and cerebrospinal fluid. Viral analysis revealed vaccine-derived poliovirus, and the child was left with lower limb paralysis.
  • In 2005, an Amish infant in Minnesota who had not been immunized with oral poliovirus before diagnosis of SCID had fever, respiratory tract infections, failure to thrive, bloody diarrhea, and anemia. A stool specimen revealed the presence of live oral polio vaccine–derived poliovirus.
  •  Altogether, 35% of this isolated community had serologic or virologic evidence of the vaccine-derived poliovirus, including the patient’s 3 siblings, who had never been immunized with either the oral poliovirus vaccine or the inactivated poliovirus vaccine.
  • Since 2009, 9 cases have been published describing rotavirus vaccine–derived infections that have threatened the health of children later discovered to have SCID.
  • V. Hernandez-Trujillo has received consultancy fees from Sanofi and Baxter; has received lecture fees from Merck, Sanofi, Baxter, and CSL; has received travel fees from Baxter; is a spokesperson for Sanofi; and is a spokesperson and member of the Claritin Council for Merck. S. Miles is a voluntary board member for a medical advisory committee.

February 13, 2014 – Associations between race, sex and immune response variations to rubella vaccination in two independent cohorts “Our replicated findings in two independent, large, racially diverse cohorts indicate that individuals of African descent have significantly higher rubella-specific neutralizing antibody levels compared to individuals of European descent and/or Hispanic ethnicity (p < 0.001).” Comment: if this is the case, they how can they advocate a one-size-fits-all policy?

February 5, 2014 – Positive Network Assortativity of Influenza Vaccination at a High School: Implications for Outbreak Risk and Herd Immunity (full text) “Our finding of gender-based differences in vaccination coverage at this particular school, with more females being vaccinated than males, is also consistent with previous reports. In this study, however, we further demonstrate that gender-based differences in vaccination status can drive overall vaccine assortativity (Fig. S6, S7; Table S6). This suggests that increasing the vaccination coverage of males in this particular network could reduce vaccination assortativity in addition to increasing overall vaccination coverage. This result has important public health implications, because thestrategies needed to increase vaccination coverage in males may be different than for females.”

December 17, 2013 – Moderate alcohol consumption enhances vaccine-induced responses in rhesus macaques “In this study, we extended these observations by investigating the impact of chronic ethanol exposure on the immune response to Modified Vaccinia Ankara (MVA). All animals were vaccinated with MVA before ethanol exposure to ethanol and then again after 7 months of 22 h/day of “open-access” drinking of 4% (w/v) ethanol. Our results indicate that animals whose blood ethanol concentration (BEC) chronically exceeded 80 mg/dl had lower CD4 and CD8 T cell proliferation as well as IgG responses following MVA booster than control animals. In contrast, relatively moderate drinkers whose BEC remained below 80 mg/ml exhibited more robust MVA-specific IgG and CD8 T cell responses than controls.”

December 15, 2013 – Maternal Supplementation with LGG Reduces Vaccine-Specific Immune Responses in Infants at High-Risk of Developing Allergic Disease. (full text) “Further clinical studies are needed to confirm these findings. As probiotic immune effects can be species/strain specific, our findings do not exclude the potential use of other probiotic bacteria to modulate infant immune responses to vaccines.”

December 5, 2013 – Vaccine Activation of the Nutrient Sensor GCN2 in Dendritic Cells Enhances Antigen Presentation “NIAID-funded Study Reveals Enzyme’s Novel Role in Immune Response to Vaccines Researchers at Emory University have shown that an enzyme involved in cellular responses to nutrient shortages also plays a role in vaccine-induced immune responses. The yellow fever vaccine and a certain type of influenza vaccine activate the enzyme, called GCN2, stimulating pathways that lead to specific immune responses. Finding ways to activate this process may lead to the development of better vaccines.

July 2013 – Conscious Consideration of Herd Immunity in Influenza Vaccination Decisions ” Overall, only 6% (28 of 442) gave a response consistent with the reduced-risk logic of herd immunity, which was more common among those stating that they would be less likely to get vaccinated (emphasizing free-riding) than among those more likely to get vaccinated (emphasizing social protection; 33% vs 11%, two-sided, p=0.0005). The reduced-risk logic of herd immunity, and more specifically free-riding, is consciously considered by relatively few individuals. Far more common are social influences bolstering personal vaccination, such as peer pressure and social learning (6% vs 11%, two-sided, p=0.015).

May 17, 2013 – The status of live viral vaccination in early lifeThe obstacles for early and neonatal vaccination are complex and include host factors, such as a developing immune system and the interference of passively acquired antibodies, as well vaccine-specific issues, such as optimal route of administration, titer and dosing requirements.

May 17, 2013 – Human immune responses to vaccines in the first year of life: Biological, socio-economic and ethical issues – A viewpoint “Although vaccines against a number of diseases exist, there are no vaccines against many other diseases that commonly affect children. The adequate assessment of immune responses to vaccines is an important step in the development of vaccines. However, a number of biological and “non-medical” socio-economic and ethical factors could influence either the administration and/or evaluation of vaccines in infants. Recognition and understanding of these determinants are crucial in planning interventions and for logical interpretations of results.”

January 21, 2013 A Population-Based Cohort Study of Undervaccination in 8 Managed Care Organizations Across the United States ” Of 323 247 children born between 2004 and 2008, 48.7% were undervaccinated for at least 1 day before age 24 months. The prevalence of undervaccination and specific patterns of undervaccination increased over time (P < .001). In a matched cohort analysis, undervaccinated children had lower outpatient visit rates compared with children who were age-appropriately vaccinated (incidence rate ratio [IRR], 0.89; 95% CI, 0.89- 0.90).”

January 7, 2013 Immune responses and protection in children in developing countries induced by oral vaccines “The detrimental effect of adverse environment and malnutrition may bring about irreversible changes in the mucosa of children especially in the first 1000 days of life from conception to after birth and up to two years of age. This review aims to summarize the information available on lowered immune responses to mucosal vaccines and on interventions that may help address the constraints of these vaccines when they are used for children living under the greatest stress and under harmful adverse circumstances.”

November 30, 2012 How Is Vaccine Effectiveness Scaled by the Transmission Dynamics of Interacting Pathogen Strains with Cross-Protective Immunity? (full text) “When it comes to multiple antigenic types, it should be noted that many diseases are caused by antigenically diverse pathogens, and more importantly, many new vaccines can only protect against infection with particular antigenic types. In such an instance, epidemiology of vaccination against a multi-strain disease involves not only the issue of limited clinical protection from a limited number of strains but also a complex epidemiological problem in scaling vaccine effectiveness by vaccination coverage and the transmission dynamics.”

November 8, 2012 Vaccines: From Empirical Development to Rational Design (full text) “Subunit vaccines are likely to lack the molecular cues needed for efficient activation of the innate immune system, thereby failing to induce vigorous adaptive immunity. PAMPs can act as adjuvants, however many pathogen-derived products might exhibit toxic activity. The only globally approved adjuvant for humans is alum. It facilitates TH2-dependent immune responses but promotes less effective cytotoxic responses and can cause side effects. A number of other adjuvants have beenrecently approved for use in defined human vaccines, such as MF59 and monophosphoryl lipid A-containing formulations [40], [41], and there are other candidates in the pipeline. Adjuvants are not licensed individually, but as part of vaccine formulations.

October 16, 2012 Systematic review of studies evaluating the broader economic impact of vaccination in low and middle income countries (pdf) “Besides herd immunity, negative ecological externalities may also occur, such as replacement of strains of pathogens eliminated by vaccination with other strains unaffected by vaccination.Comment: This is saying that vaccines can eliminate one strain but other more virulent strains can take its place.

August 27, 2012 – The Role of Herd Immunity in Parents’ Decision to Vaccinate Children: A Systematic Review “There appears to be some parental willingness to immunize children for the benefit of others, but its relative importance as a motivator is largely unknown. Further work is needed to explore this concept as a possible motivational tool for increasing childhood immunization uptake.”

June 2012 – Vaccination and herd immunity: what more do we know? “The conventional idea of herd immunity is based on the relationship between the transmission dynamics of infectious agents and population immunity. However, there have been some recent conceptual developments in vaccine ‘herd immunity’ or ‘herd protection’ that address the complexities of imperfect immunity, heterogeneous populations, nonrandom vaccine uptake and ‘freeloaders’. Summary: Herd immunity is a complex issue inherent to an individual vaccine and the population receiving the vaccine.

May 7, 2012 – Exploiting Temporal Network Structures of Human Interaction to Effectively Immunize Populations (full text) “Decreasing the number of people who must be vaccinated to immunize a community against an infectious disease could both save resources and decrease outbreak sizes. A key to reaching such a lower threshold of immunization is to find and vaccinate people who, through their behavior, are more likely than average to become infected and to spread the disease further. Fortunately, the very behavior that makes these people important to vaccinate can help us to localize them.”

February 2012The concept of vaccination failure “Despite remarkable success of immunization programmes on a global perspective, vaccines are neither 100% efficacious nor 100% effective. Therefore, vaccination failure, i.e. occurrence of a specific disease in an individual despite previous vaccination, may occur. Vaccination failure may be due to actual vaccine failure or failure to vaccinate appropriately.

January 25, 2012 Serum Vaccine Antibody Concentrations in Children Exposed to Perfluorinated Compounds “Elevated exposures to PFCs were associated with reduced humoral immune response to routine childhood immunizations in children aged 5 and 7 years.”

July 12, 2011 – Why Isn’t ‘Herd Immunity’ Working? By Catherine J. Frompovich

June 2011New approaches to the assessment of vaccine herd protection in clinical trials

November 1, 2011 Kinetics of the Antibody Response to Tetanus-Diphtheria-Acellular Pertussis Vaccine in Women of Childbearing Age and Postpartum Women

October 19, 2011 Associations between single nucleotide polymorphisms and haplotypes in cytokine and cytokine receptor genes and immunity to measles vaccination “Multiple IL7R polymorphisms, including a non-synonymous functional SNP (rs6897932/Thr244Ile), were associated with humoral (p ≤ 0.024) and/or cellular (IFNγ Elispot, p ≤ 0.023) measles-specific immune responses in Caucasians, but not African-Americans. Haplotype level analysis confirmed the association of IL7R genetic variants with measles vaccine-induced immunity in the Caucasian group (global p-value = 0.003). Our results validate previous findings and identify new plausible genetic determinants, including IL7R polymorphisms, regulating measles vaccine-induced immunity in a race-specific manner.”

October 13, 2011 Presence of immune memory and immunity to hepatitis B virus in adults after neonatal hepatitis B vaccination “The adults received neonatal HBV vaccination had immune memory and immunity against HBV infection. However, 31.9% of neonatal HBV vaccinees who responded weakly at an early age might be susceptible to HBV infection after childhood.”

October 2011
Human leukocyte antigen associations with humoral and cellular immunity following a second dose of measles-containing vaccine: Persistence, dampening, and extinction of associations found after a first dose “It appears that the second dose overcomes HLA restriction through an as yet unknown mechanism. Future studies of HLA associations should consider both the effect of dose and the role that subsequent doses might play on genetic associations found with the response to a first dose.”

October 2011 Varicella Immunity in Inflammatory Bowel Disease “Lack of varicella immunity is common in children and adolescents at the time of diagnosis of IBD. Routine screening for varicella immune status may be warranted. Offering immunization to susceptible patients should confer protection, but this may be difficult to achieve once immune suppression has begun.”

July 2011 Immunogenicity, Boostability, and Sustainability of the Immune Response after Vaccination against Influenza A Virus (H1N1) 2009 in a Healthy Population “A single dose of the 2009 vaccine was immunogenic in almost 80% of the study population, whereas an additional dose resulted in significantly increased titers only in persons over 50. Finally, a reduced HI antibody response against the 2009 vaccine was found in adults who had previously received seasonal influenza virus vaccination. More studies on the effect of yearly seasonal influenza virus vaccination on the immune response are warranted.”

July 2011 Meningococcal Group C and W135 Immunological Hyporesponsiveness in African Toddlers “Immunologic hyporesponsiveness for groups C and W135 was observed following a full dose of PsACWY vaccine at 12 to 23 months of age and a 1/5 dose of PsACWY 10 months later compared to the case for PsACWY-naïve subjects receiving a 1/5 dose of PsACWY vaccine.”

July 2011 Persistence of Rabies Antibody 5 Years after Postexposure Prophylaxis with Vero Cell Antirabies Vaccine and Antibody Response to a Single Booster Dose

May-June 2011 Prevalence of Antibodies Associated With Herd Immunity A Comment “This note identifies and describes 4 major problems with the methodological approach taken by Plans. First, to apply the formula correctly, Plans should have compared the critical value I c with actual vaccine coverage data from Catalonia, Spain. Unfortunately, the author mistakenly equated prevalence of antibodies with the proportion of new recruits successfully vaccinated. Clearly the 2 quantities are different because the proportion of the population with antibodies also includes persons who have acquired antibodies through natural infection. Because the mix of antibodies acquired through natural infection or vaccination changes with the age and coverage of the vaccination program, the indicator proposed by Plans is valid only in the long term.”

July/August 2010 Prevalence of Antibodies Associated with Herd Immunity: A New Indicator to Evaluate the Establishment of Herd Immunity and to Decide Immunization Strategies “Results. The herd immunity was not established (p < pc) against measles, mumps, and varicella in schoolchildren aged 6 to 9 years, against measles in individuals aged 15 to 24 years, and against pertussis in all age groups. Based on these results, the measles-mumps-rubella (MMR) vaccine should be given to schoolchildren and individuals aged 15 to 24 years, the varicella vaccine to schoolchildren aged 6 to 9 years, and the diphtheria-tetanus-pertussis (DTaP/dTaP) vaccine to all age groups in order to establish the necessary herd immunity in the population.”

November 2009Vaccination of healthy subjects and autoantibodies: from mice through dogs to humans “At present there is no clear-cut evidence that vaccinations are associated with overt autoimmune diseases but it has been demonstrated that in genetically predisposed persons vaccination can trigger the production of autoantibodies and autoimmune adverse reactions. The first studies investigating the production of autoantibodies following vacination were done in dogs and mice. Several studies investigated the production of autoantibodies following vaccination in patients with autoimmune diseases, but there are only limited data on the autoimmune responses after vaccinations in apparently healthy humans. This review summarizes current evidence on the vaccination induced autoantibodies in apparently healthy subjects including studies in animals and humans.”

November 2009 – Adjuvants and autoimmunity. “The debatable question of silicone as an adjuvant and connective tissue diseases, as well as the Gulf War syndrome and macrophagic myofaciitis which followed multiple injections of aluminium-based vaccines, are presented here.”

February 1, 2005 Role of Herd Immunity in Determining the Effect of Vaccines against Sexually Transmitted Disease

July 5, 2002 Is the theory of “herd immunity” flawed? by Sandy Gottstein

August 1999 A hepatitis B virus variant found in the sera of immunised children induces a conformational change in the HBsAg “a” determinant. “The implications of this work are that serodiagnosis of HBV infections may be unreliable in populations where there is a possibility of variant HBV infections emerging in the face of increasing herd immunity to HBV as a result of vaccination, particularly using monoclonal antibody-based diagnostic tests.”

1997Measles antibodies and herd immunity in 20- and 40-year-old Norwegians.

April 1989 Natural or vaccine-induced antibody as a predictor of immunity in the face of natural challenge with influenza viruses. (full text)

January 11, 1973Failure of Rubella Herd Immunity during an Epidemic “The concept that a highly immune group of prepubertal children will prevent the spread of rubella in the rest of the community was shown by this epidemic not always to be valid.”