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Vaccination Failure

Published: 2023
SYNOPSIS

Vaccines can have beneficial off-target (heterologous) effects that alter immune responses to, and protect against, unrelated infections. The heterologous effects of COVID-19 vaccines have not been investigated in children.

TITLE

BNT162b2 COVID-19 vaccination in children alters cytokine responses to heterologous pathogens and Toll-like receptor agonists

A. Noé, T. D. Dang, C. Axelrad, E. Burrell, S. Germano, S. Elia, D. Burgner, K. P. Perrett, N. Curtis, N. L. Messina

In addition to antigen-specific adaptive immunity to the target pathogen and cross-protective immunity to related microbes (e.g., protection against Mycobacterium tuberculosis and Mycobacterium leprae induced by Mycobacterium bovis-derived bacille Calmette–Guérin (BCG)) (1), vaccines have off-target (heterologous) effects that protect against unrelated pathogens (24).

In high-mortality settings, live-attenuated vaccines are associated with reductions in all-cause infant mortality greater than can be attributed to vaccine-specific protection alone (57). The reduction in all-cause mortality in high-mortality settings is proposed to be due, at least in part, to protection against infections unrelated to the vaccine target (24). Trained immunity, the process by which innate immune cells such as monocytes develop immunological memory through metabolic and epigenetic changes, is one proposed mechanism by which vaccines exert heterologous effects (8, 9). Understanding heterologous effects and trained immunity, and harnessing positive heterologous effects has the potential to extend vaccine-induced protection to a diverse array of pathogens.

The COVID-19 pandemic has prompted a resurgence of interest in the heterologous effects of BCG and other vaccines and compounds (1014). Heterologous immunological effects following vaccination have been explored in several studies by assessing in vitro cytokine responses to heterologous antigens (9, 1519). Two small studies have reported on heterologous effects of COVID-19 vaccines. One study in adults reported that following adenoviral COVID-19 (ChAdOx1) vaccination, monocyte proinflammatory cytokine and chemokine production and glycolysis is enhanced in resting states as well as in response to unrelated stimulants (20). COVID-19 mRNA-based vaccines have been reported to modulate transcriptional profiles in monocytes from adults (21). To date, the heterologous effects of COVID-19 vaccines have not been investigated in children.

In the COVID-19-Specific vaccine and heterologous Immunity in MIS BAIR (COSI BAIR) study (22), we investigated the heterologous and specific immunological effects of BNT162b2 COVID-19 vaccination in children.

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Published: 2022
SYNOPSIS

Persistent exposure to faecal pathogens due to open defecation may cause environmental enteropathy that, in turn, may lead to undernutrition and vaccine failure in under 5-year-old (u5) children.

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Association between vaccine preventable diseases in children and improved sanitation following a nationwide sanitation campaign in India: an ecological analysis

P. Singh, D. N. Forthal, M. Shah, T.A. Bruckner

Persistent exposure to faecal pathogens due to open defecation may cause environmental enteropathy that, in turn, may lead to undernutrition and vaccine failure in under 5-year-old (u5) children. The Swachh Bharat Mission (SBM) programme in India, launched in 2014, aimed to construct toilets for every household nationwide and reduce open defecation. This programme, if successful, had the potential to reduce the burden of four vaccine preventable diseases (VPDs): diphtheria, pertussis, tetanus and measles. We examine whether increased household toilet availability in Indian districts following SBM corresponds with a reduction in diphtheria, pertussis, tetanus and measles in u5 children.

 

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Published: 2019
SYNOPSIS

Waning levels of measles antibodies with increasing time post-vaccination suggests that measles susceptibility is potentially increasing in Korea.

TITLE

An increasing, potentially measles-susceptible population over time after vaccination in Korea

CITATION

Kang, H. J., et al. Vaccine, 35 (2017) 4126–4132.

SUMMARY

In Korea, measles occurs mainly in infants <12 months of age, who are unvaccinated. In
addition, vaccine populations, including adolescents and young adults, can become infected through importation. Thus, the question arises whether the current level of herd immunity in Korea is now insufficient for protecting against measles infection.

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Published: 2019
SYNOPSIS

About 2%–10% of healthy individuals fail to mount antibody levels to routine vaccines.

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Primary vaccine failure to routine vaccines: Why and what to do?

CITATION

Wiedermann U, Garner-Spitzer E, Wagner A. Human Vaccines & Immunotherapeutics. 2016;12(1):239–243.

SUMMARY

Two sets of factors are responsible for vaccine failure: vaccine-related factors (e.g., failures in vaccine attenuation, vaccination regimes or administration) and host-related factors (e.g., genetics, immune status, age, health or nutritional status). Primary vaccine failure describes the inability to respond to primary vaccination, and secondary vaccine failure is characterized by a loss of protection after initial effectiveness. Studies indicate that about 2%–10% of healthy individuals fail to mount antibody levels to routine vaccines. T-regulatory as well as B-regulatory cells and the production of IL-10 are involved in non/hypo-responsiveness to vaccination. Non-responsiveness increases with age, indicating that vaccine schedules and doses (at least for primary vaccination) should be adapted according to age. Studies also suggest that different vaccination approaches may be needed for allergic or obese individuals. The significant paradigm shift taking place in many fields of medical research and care should extend the concept of personalized medicine into the field of vaccinology.

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Published: 2019
SYNOPSIS

Outbreaks of measles can occur in secondary schools, even when more than 99 percent of the students have been vaccinated and more than 95 percent are immune.

TITLE

Measles outbreak in a fully immunized secondary-school population.

CITATION

Gustafson TL, Lievens AW, Brunell PA, Moellenberg RG, Buttery CM, Sehulster LM. New England Journal of Medicine, 1987 Mar 26;316(13):771-4.

SUMMARY

An outbreak of measles occurred among adolescents in Corpus Christi, Texas, in the spring of 1985, even though vaccination requirements for school attendance had been thoroughly enforced. Serum samples from 1806 students at two secondary schools were obtained eight days after the onset of the first case. Only 4.1 percent of these students (74 of 1806) lacked detectable antibody to measles according to enzyme-linked immunosorbent assay, and more than 99 percent had records of vaccination with live measles vaccine. Stratified analysis showed that the number of doses of vaccine received was the most important predictor of antibody response. Ninety-five percent confidence intervals of seronegative rates were 0 to 3.3 percent for students who had received two prior doses of vaccine, as compared with 3.6 to 6.8 percent for students who had received only a single dose. After the survey, none of the 1732 seropositive students contracted measles. Fourteen of 74 seronegative students, all of whom had been vaccinated, contracted measles. In addition, three seronegative students seroconverted without experiencing any symptoms. We conclude that outbreaks of measles can occur in secondary schools, even when more than 99 percent of the students have been vaccinated and more than 95 percent are immune.

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Published: 2018
SYNOPSIS

In Israel in 2017, nine measles cases were identified in a population with high measles vaccination coverage.

TITLE

Measles Outbreak in a Highly Vaccinated Population – Israel, July-August 2017

Citation

Avramovich E, Indenbaum V, Haber M, Amitai Z, Tsifanski E, Farjun S, Sarig A, Bracha A, Castillo K, Markovich MP, Galor I. MMWR Morbidity and Mortality Weekly Report. 2018 Oct 26;67(42):1186-1188.

Summary

On August 6, 2017, the Israeli Defense Force Public Heath Branch (IDFPHB) was notified of two suspected measles cases. IDFPHB conducted an epidemiologic investigation, which identified nine measles cases in a population with high measles vaccination coverage. All measles patients had signs and symptoms consistent with modified measles (i.e., less severe disease with milder rash, fever, or both, with or without other mild typical measles symptoms). A total of 1,392 contacts were identified, and 162 received postexposure prophylaxis (PEP) with measles-mumps-rubella (MMR) vaccine; the remaining contacts were followed for 21 days (one incubation period). No tertiary cases were identified.

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Published: 2014
SYNOPSIS

These data provide a plausible explanation for pertussis resurgence and suggest that attaining herd immunity will require the development of improved vaccination strategies that prevent B. pertussis colonization and transmission.

TITLE

Acellular pertussis vaccines protect against disease but fail to prevent infection and transmission in a nonhuman primate model

CITATION

Jason M. Warfel, Lindsey I. Zimmerman, and Tod J. Merkel; Proceedings of the National Academy of Sciences; January 14, 2014, 111 (2), 787-792; https://doi.org/10.1073/pnas.1314688110.

SUMMARY

In this study, researchers found that current acellular pertussis (aP) vaccines fail to prevent colonization and transmission. Nonhuman primates vaccinated with current acellular Pertussis (aP) were protected from severe symptoms but not infection and readily transmitted Bordetella pertussis to contacts.

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Published: 2010
SYNOPSIS

Acellular Pertussis vaccination interferes with the optimal clearance of B. parapertussis and enhances the performance of this pathogen. Our data raise the possibility that widespread acellular Pertussis vaccination can create hosts more susceptible to B. parapertussis infection.

TITLE

Acellular pertussis vaccination facilitates Bordetella parapertussis infection in a rodent model of bordetellosis

CITATION

Gráinne H. Long, Alexia T. Karanikas, Eric T. Harvill, Andrew F. Read and Peter J. Hudson, Proceedings of the Royal Society B, Biological Sciences; 03 March, 2010; Volume 277; https://doi.org/10.1098/rspb.2010.0010

SUMMARY

Despite over 50 years of population-wide vaccination, whooping cough incidence is on the rise. Although Bordetella pertussis is considered the main causative agent of whooping cough in humans, Bordetella parapertussis infections are not uncommon. The widely used acellular whooping cough vaccines (aP) are comprised solely of B. pertussis antigens that hold little or no efficacy against B. parapertussis. Here, we ask how aP vaccination affects competitive interactions between Bordetella species within co-infected rodent hosts and thus the aP-driven strength and direction of in-host selection. We show that aP vaccination helped clear B. pertussis but resulted in an approximately 40-fold increase in B. parapertussis lung colony-forming units (CFUs). Such vaccine-mediated facilitation of B. parapertussis did not arise as a result of competitive release; B. parapertussis CFUs were higher in aP-relative to sham-vaccinated hosts regardless of whether infections were single or mixed. Further, we show that aP vaccination impedes host immunity against B. parapertussis—measured as reduced lung inflammatory and neutrophil responses. Thus, we conclude that aP vaccination interferes with the optimal clearance of B. parapertussis and enhances the performance of this pathogen. Our data raise the possibility that widespread aP vaccination can create hosts more susceptible to B. parapertussis infection.

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Published: 2006
SYNOPSIS

Repeated influenza vaccination at a young age substantially increases the risk of influenza at older ages.

TITLE

Repeated influenza vaccination of healthy children and adults: borrow now, pay later?

CITATION

Carrat F, Lavenu A, Cauchemez S, Deleger S. Repeated influenza vaccination of healthy children and adults: borrow now, pay later? Epidemiology & Infection 2006;134(1):63-70.

SUMMARY

This study shows that repeated influenza vaccination at younger ages may double the risk of influenza in the elderly. The study suggests that the “possible benefits of vaccinating children after 5 years of age, and otherwise healthy adults—particularly over a long period and mainly for economic reasons—could be outweighed by severe clinical consequences and increased costs in the elderly.” Moreover, the findings are “solely due to differences between vaccine-induced immunity and naturally acquired immunity.” Unlike vaccination, naturally acquired immunity can provide long-lasting protection against subsequent infection by the same viral subtype.

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Published: 1984
SYNOPSIS

A computer model was created to study the effect of the measles elimination program in the United States on the number of susceptibles in the population. The simulation reveals that in the prevaccine era, approximately 10.6% of the population was susceptible to measles, most of whom were children less than 10 years of age.

TITLE

The future of measles in highly immunized populations. A modeling approach.

CITATION

Levy DL. American Journal of Epidemiology. 1984 Jul;120(1):39-48.

SUMMARY

Little is known about how an intensive measles elimination program changes the overall immune status of the population. A computer model was created to study the effect of the measles elimination program in the United States on the number of susceptibles in the population. The simulation reveals that in the prevaccine era, approximately 10.6% of the population was susceptible to measles, most of whom were children less than 10 years of age. With the institution of the measles immunization program, the proportion of susceptibles in the population fell to 3.1% from 1978 through 1981, but then began to rise by approximately 0.1% per year to reach about 10.9% in the year 2050. The susceptibles at this time were distributed evenly throughout all age groups. The model did not consider the potential effect of waning immunity. The results of this study suggest that measles elimination in the United States has been achieved by an effective immunization program aimed at young susceptibles combined with a highly, naturally immunized adult population. However, despite short-term success in eliminating the disease, long-range projections demonstrate that the proportion of susceptibles in the year 2050 may be greater than in the prevaccine era. Present vaccine technology and public health policy must be altered to deal with this eventuality.

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Published: 1982
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The 1989 measles outbreak in the province of Quebec has been largely attributed to an incomplete vaccination coverage, despite a 99% vaccination rate.

TITLE

Major measles epidemic in the region of Quebec despite a 99% vaccine coverage

Citation

Boulianne N, De Serres G, Duval B, Joly JR, Meyer F, Déry P, Alary M, Le Hénaff D, Thériault N. Canadian Journal of Public Health. 1991 May-Jun;82(3):189-90.

Summary

The 1989 measles outbreak in the province of Quebec has been largely attributed to an incomplete vaccination coverage. In the Quebec City area (pop. 600,000) 1,363 confirmed cases of measles did occur. A case-control study conducted to evaluate risk factors for measles allowed us to estimate vaccination coverage.  The vaccination coverage among cases was at least 84.5%. Vaccination coverage for the total population was 99.0%. Incomplete vaccination coverage is not a valid explanation for the Quebec City measles outbreak.

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