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  • Vaccines have sex differential non-targeted heterologous effects: a new dawn in vaccine research

    Trans R Soc Trop Med Hyg (2015) 109 (1): 1-2. doi: 10.1093/trstmh/tru188
    Vaccines have sex differential non-targeted heterologous effects: a new dawn in vaccine research
    Katie L. Flanagan Key words



    Next Section
    The WHO Strategic Advisory Group of Experts (SAGE) on immunization recently published their conclusions from a systematic review of the ?non-specific? or ?heterologous effects? of vaccines, hailing a new era in our understanding of what vaccines do to the immune system.1 The report recognizes that bacille Calmette-Gu?rin (BCG) vaccine and measles vaccine (MV) may provide survival benefits against infectious diseases other than those targeted by the vaccine. These non-specific or heterologous effects of vaccines, whereby vaccines alter susceptibility to infections other than that targeted by the vaccine, can be beneficial as is the case for BCG and MV; but other vaccines such as diphtheria-tetanus-pertussis (DTP) vaccine may increase susceptibilty to infections, although WHO conclude that the data supporting deleterious effects of DTP are inconclusive.1 As a rule females seem to be more susceptible to these vaccine-induced heterologous effects than males.2,3
    http://trstmh.oxfordjournals.org/content/109/1/1.full


    Trans R Soc Trop Med Hyg (2015) 109 (1): 77-84. doi: 10.1093/trstmh/tru186
    ]Sex-differential and non-specific effects of routine vaccinations in a rural area with low vaccination coverage: an observational study from Senegal
    Results At 12 months the vaccination coverage was 44%, 46% and 9%, respectively, for BCG, DTP1 and MV. Most children received BCG+DTP1-first and this combination was associated with a significantly lower mortality rate ratio (MRR) of 0.69 (0.53?0.89) compared with unvaccinated children. There was no benefit for children receiving BCG-first or DTP1-first. The female-male MRR was 0.79 (0.64?0.96) among unvaccinated children, but was significantly inversed with 1.45 (1.00?2.10) for children receiving DTP vaccination (test of homogeneity, p=0.006). Children who had received DTP simultaneously with MV or DTP after MV had significantly higher mortality (MRR=2.59 [1.32?5.07]) compared with children having MV-only as their most recent vaccination. After 9 months, the female-male MRR was 0.61 (0.31?1.19) for measles-vaccinated children but remained 1.54 (1.03?2.31) for DTP-vaccinated children who had not received MV (p=0.01).

    Conclusions The sequence of routine vaccinations is important for the overall impact on child survival and these vaccines are associated with sex-differential effects.
    http://trstmh.oxfordjournals.org/con.../1/77.abstract
    _____________________________________________

    Ask Congress to Investigate COVID Origins and Government Response to Pandemic H.R. 834

    i love myself. the quietest. simplest. most powerful. revolution ever. ---- nayyirah waheed

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  • #2
    http://ije.oxfordjournals.org/conten...je.dyv117.full
    Original Paper:
    • Christine S Benn,
    • Peter Aaby,
    • Rob JW Arts,
    • Kristoffer J Jensen,
    • Mihai G Netea,
    • and Ane B Fisker

    An enigma: why vitamin A supplementation does not always reduce mortality even though vitamin A deficiency is associated with increased mortality Int. J. Epidemiol. first published online July 2, 2015 doi:10.1093/ije/dyv117
    Abstract

    Background: Vitamin A deficiency (VAD) is associated with increased mortality. To prevent VAD, WHO recommends high-dose vitamin A supplementation (VAS) every 4–6 months for children aged between 6 months and 5 years of age in countries at risk of VAD. The policy is based on randomized clinical trials (RCTs) conducted in the late 1980s and early 1990s. Recent RCTs indicate that the policy may have ceased to be beneficial. In addition, RCTs attempting to extend the benefits to younger children have yielded conflicting results. Stratified analyses suggest that whereas some subgroups benefit more than expected from VAS, other subgroups may experience negative effects.
    Methods and Results: We reviewed the potential modifiers of the effect of VAS. The variable effect of VAS was not explained by underlying differences in VAD. Rather, the effect may depend on the sex of the child, the vaccine status and previous supplementation with vitamin A. Vitamin A is known to affect the Th1/Th2 balance and, in addition, recent evidence suggests that vitamin A may also induce epigenetic changes leading to down-regulation of the innate immune response. Thus VAS protects against VAD but has also important and long-lasting immunological effects, and the effect of providing VAS may vary depending on the state of the immune system.
    Conclusions: To design optimal VAS programmes which target those who benefit and avoid those harmed, more studies are needed. Work is ongoing to define whether neonatal VAS should be considered in subgroups. In the most recent RCT in older children, VAS doubled the mortality for males but halved mortality for females. Hence, we urgently need to re-assess the effect of VAS on older children in large-scale RCTs powered to study effect modification by sex and other potential effect modifiers, and with nested immunological studies.
    Key words
    Key Messages
    • Vitamin A deficiency is associated with increased mortality from infectious diseases, and to prevent vitamin A deficiency, high-dose vitamin A capsules are recommended twice per year to children between 6 months and 5 years of age in more than 100 countries considered at risk of vitamin A deficiency.
    • The effect of vitamin A supplementation is assumed to be always beneficial, reducing deaths due to vitamin A deficiency.
    • A number of observations contradict the interpretation that vitamin A supplementation acts merely to prevent vitamin A deficiency. The effect of vitamin A supplementation is not associated with the degree of deficiency, and the effect is modified by factors unrelated to deficiency, such as sex of the child and the vaccines he or she has received.
    • The existing evidence supports that besides preventing vitamin A deficiency, vitamin A supplementation also has long-lasting immunological effects; and, worryingly, the effect of vitamin A supplementation may be harmful in some subgroups.
    • To create optimal vitamin A supplementation policies, we urgently need to re-assess the effect of vitamin A supplementation in large-scale RCTs powered to study effect modification by sex and other potential effect modifiers, and with nested immunological studies.

    _____________________________________________

    Ask Congress to Investigate COVID Origins and Government Response to Pandemic H.R. 834

    i love myself. the quietest. simplest. most powerful. revolution ever. ---- nayyirah waheed

    (My posts are not intended as advice or professional assessments of any kind.)
    Never forget Excalibur.

    Comment


    • #3
      http://trstmh.oxfordjournals.org/content/109/1/29.short
      Vaccines have sex differential non-targeted heterologous effects: a new dawn in vaccine research Trans R Soc Trop Med Hyg (2015) 109 (1): 1-2
      Abstract

      A growing body of evidence from epidemiologic and immunologic studies have shown that in addition to target disease-specific effects, vaccines have heterologous effects towards unrelated pathogens. Like some other vaccines, bacille Calmette-Guerin (BCG) has shown in observational studies and randomized clinical trials to increase survival beyond the disease burden of the target disease. The immunologic substrate for these non-specific protective effects have been ascertained to heterologous T cell effects on the one hand, and to priming of innate immunity on the other hand. The term 'trained immunity' has been proposed to describe these potentiating effects of vaccines on innate immune responses. This process can explain the rapid effects of BCG vaccination and has been suggested to be mediated by epigenetic programming of monocytes or macrophages. This novel concept has important implications for the possible use of vaccines, for vaccination policy and even for the design of novel immunotherapeutic approaches.
      ? The Author 2015. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.


      KEYWORDS:

      BCG; Heterologous effects; Innate immunity; Trained immunity; Vaccine

      _____________________________________________

      Ask Congress to Investigate COVID Origins and Government Response to Pandemic H.R. 834

      i love myself. the quietest. simplest. most powerful. revolution ever. ---- nayyirah waheed

      (My posts are not intended as advice or professional assessments of any kind.)
      Never forget Excalibur.

      Comment


      • #4
        http://trstmh.oxfordjournals.org/con.../1/62.abstract
        • Anna Gil,
        • Laurie L. Kenney,
        • Rabinarayan Mishra,
        • Levi B. Watkin,
        • Nuray Aslan,
        • and Liisa K. Selin

        Vaccination and heterologous immunity: educating the immune system Trans R Soc Trop Med Hyg (2015) 109 (1): 62-69 doi:10.1093/trstmh/tru198 Abstract

        This review discusses three inter-related topics: (1) the immaturity of the neonatal and infant immune response; (2) heterologous immunity, where prior infection history with unrelated pathogens alters disease outcome resulting in either enhanced protective immunity or increased immunopathology to new infections, and (3) epidemiological human vaccine studies that demonstrate vaccines can have beneficial or detrimental effects on subsequent unrelated infections. The results from the epidemiological and heterologous immunity studies suggest that the immune system has tremendous plasticity and that each new infection or vaccine that an individual is exposed to during a lifetime will potentially alter the dynamics of their immune system. It also suggests that each new infection or vaccine that an infant receives is not only perturbing the immune system but is educating the immune system and laying down the foundation for all subsequent responses. This leads to the question, is there an optimum way to educate the immune system? Should this be taken into consideration in our vaccination protocols?
        _____________________________________________

        Ask Congress to Investigate COVID Origins and Government Response to Pandemic H.R. 834

        i love myself. the quietest. simplest. most powerful. revolution ever. ---- nayyirah waheed

        (My posts are not intended as advice or professional assessments of any kind.)
        Never forget Excalibur.

        Comment


        • #5
          http://jama.jamanetwork.com/article....&resultclick=3
          Original Investigation | February 26, 2014

          Live Vaccine Against Measles, Mumps, and Rubella and the Risk of Hospital Admissions for Nontargeted Infections FREE
          Signe S?rup, PhD1; Christine S. Benn, DMSc1,2,3; Anja Poulsen, PhD4; Tyra G. Krause, PhD5; Peter Aaby, DMSc1,3; Henrik Ravn, PhD1,3
          [+] Author Affiliations
          JAMA. 2014;311(8):826-835. doi:10.1001/jama.2014.470 ABSTRACT

          Importance In low-income countries, live measles vaccine reduces mortality from causes other than measles infection. Such nonspecific effects of vaccines might also be important for the health of children in high-income settings.
          Objective To examine whether the live vaccine against measles, mumps, and rubella (MMR) is associated with lower rates of hospital admissions for infections among children in Denmark.

          ...

          Conclusions and Relevance In a cohort of Danish children, receipt of live MMR vs inactivated DTaP-IPV-Hib as the most recent vaccine was associated with a lower rate of hospital admissions for any infections. These findings require replication in other high-income populations.
          _____________________________________________

          Ask Congress to Investigate COVID Origins and Government Response to Pandemic H.R. 834

          i love myself. the quietest. simplest. most powerful. revolution ever. ---- nayyirah waheed

          (My posts are not intended as advice or professional assessments of any kind.)
          Never forget Excalibur.

          Comment

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