8 July 2021 Episode 152 : Updates on HIV-COVID, vaccination in children and intradermal COVID vaccines.

Thu, 07/08/2021 - 19:46

Dear colleagues,

While I’m preparing an episode on auto-immunity and COVID, I received some questions and comments from some of you.  Herewith I share my reflections on those with all of you.

  1. HIV and COVID:

Ep 152-1: Interesting review with nice didactic summary on p.8

While early small studies on well-treated HIV patients in Europe and US suggested that there is no interaction, larger studies, especially in South-Africa, showed that HIV-patients with low CD4 T counts and uncontrolled viral replication, suffered more severe disease and also a two times higher mortality. This is not surprising as HIV infection is associated with “immune ageing” and immune activation.

Moreover, HIV infected subjects often have more cardiovascular and metabolic co-morbidities.  Alternative etiologies or superinfections with Pneumocystis and Cryptococcus have to be considered.

In limited resource setting, prevention and treatment of HIV may be jeopardized by COVID-related measures. HIV treatment should be continued during COVID disease to prevent worsening of immune suppression.  However, there is no clear evidence that ART has a therapeutic effect on COVID.  

HIV infected subjects should be preferentially vaccinated against COVID.  Their response to vaccination needs to be monitored.  

  1. Why vaccinate children against COVID-19?

Personally, we are happy that Belgium will invite 12-15 years adolescents to be vaccinated with Pfizer. 

Ep 152-2:  An overview in JAMA on 1116 hospitalized children and adolescents, approximately 50-50 with MISC or "just" severe COVID.

  • More than a third ended up in intensive care with serious heart and lung problems. 18 children (10 MISC, 8 severe COVID) did not survive.
  • That percentage of mortality (1.6%) is of course much lower than in hospitalized adults where at least 20% do not survive, but we can nevertheless assume that all 18 deaths from this series (and the 326 American dead children in total) can be prevented by vaccination

Ep 152-3: an article in the NYT that appeared 1 day after our “Opinion” in De Morgen, with essentially the same content as shown in the summarizing sentence: Getting young people, including children, vaccinated is also critical to reaching high levels of Covid protection, and it will help prevent the spread of the coronavirus among other vulnerable adults and the emergence of more variants

 

The paper also weighs the risks of vaccination (especially transient heart muscle inflammation or myocarditis) against the risk of COVID infection in minors.

  • So far, among the 6.14 million young people under 17 vaccinated with Pfizer in US 653 have been hospitalized with myocarditis or something else after vaccination. Apparently they are all discharged healthy after 1-3 days. Extrapolating: if all 73 million young Americans are vaccinated, you can expect 7,700 short hospitalizations.
  • On the other hand 326 young people in the US have died from COVID-19 and none from vaccination. The number of expected hospitalizations if the 73 million US youth do not get vaccinated is 14,600 of which a third would require intensive care.

Hospitalization for COVID itself (as compared to after vaccination) is therefore not only more frequent, but also longer and above all with more complications, also with regard to the heart.

 

  1. Is the intradermal route an interesting alternative for COVID vaccination?

According to published data the INO 4800 DNA is most advanced: it is applied intradermally followed by in vivo electroporation.  It is a highly optimized DNA sequence encoding SARS-CoV-2 spike was created using Inovio’s proprietary in silico Gene Optimization Algorithm

Ep 152-3 A: It is tested in Chinese macaques with 1 mg on week 0 and 4

  • Induces very decent neutralization titers against “pseudoviruses” and also T cell responses (IFN-g ELISPOT). See Fig 1 D-E and H p. 26
  • The intranasal + intratracheal challenge experiment on week 17 shows a very partial protection (last page)

Ep 152-3B: In the phase 1 study in humans also 1 or 2 mg are used on week 0 and 4:

The abstract does say that there were good responses in all subjects, but if you look at Fig 3, you see that the neut titer (against fully infectious virus) is avg 1/64, which is well below the titers of the mRNA and Adeno or even inactivated vaccines. Also the T cells are weak: 32 IFN-g producing per million (Fig 4A).  It seems to be under-dosed.

Other very early attempts for ID immunization:

Ep 152-4: Yvdav compares immunogenicity of prime-boost 40 µg receptor-binding domain based peptide vaccine with Addavax (squalene-based oil-in-water adjuvant) after intradermal (ID) and intramuscular (IM) immunization in mice: responses after ID and IM were similar.

Ep 152-5: Karakus shows that gamma-irradiation of SARS-CoV-2 can be used to produce an inactivated vaccine together with granulocyte-monocyte colony stimulating factor (GM-CSF) for intradermal immunization in mice.  This ID vaccine resulted in induction of neutralizing antibodies and specific T cells.  No comparison is made with IM.

Ep 152-6:  Kuwentrai uses the recombinant Nucleoprotein +  Aluminium hydroxide gel: the interesting permutation is the use of dissolvable microneedles in mice: a very potent B and T cell response is induced, but neutralization titers are not shown (unlikely to be present, since there is no Spike protein in the preparation).

Clearly, this setting seems rather based on the presumption that T and B immunity to nucleoprotein (in addition to anti-S?) could be useful in vaccination.   

Ep 152-7:   Qingmei Jia present a very experimental vaccine, based on an attenuated tularemia bacterium (LVS ΔcapB), which, according to the authors, has previously been used to express various bacterial antigens of tularemia, anthrax, plague, and melioidosis and protect animals against lethal respiratory challenge with either of these bacteria.

Here, they produce vaccines expressing Spike (S), Membrane (M) and/or Nucleoproteins (N) of SARS-CoV-2 and apply them intranasally or intradermally in hamsters before challenge with live SARS-CoV-2.

Remarkably, whereas the spike containing vaccines were not protective, those containing M and N were partly protective against viral load, lung pathology and weight loss

 

Finally, there is an announcement of the University of Leiden that they are testing an ID application of the mRNA vaccine of Moderna, where 1/10 of the IM dosis would induce similar antibody levels!

https://www.lumc.nl/over-het-lumc/nieuws/2021/juni/onderzoek-huidprik-veelbelovend/?setlanguage=Dutch&setcountry=nl

Sorry, this site is in Dutch.  You find a translation under Ep 152-8 (Word file)

 

Best wishes,

Guido

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