New research shows that, although unvaccinated children produce antibodies and killer T-cells in response to COVID-19 infection, this response may not be strong enough to protect them against future variants, especially if the antibodies fail to recognise the variant.
The normal response to viral infections is two-fold. First there are the antibodies that are produced in response to the foreign proteins. These bind to the viruses, deactivate them and cause them to clump together so they can be moped up by phagocytic white cells. However, they can only act against circulating viruses and not against viruses that have already gained access to the cells, where they will be replicating.
The second response is the more long-term one. This produces pre-programmed killer T-lymphocytes or 'memory' T-cells - white blood cells - that recognise infected cells and destroy them, together with the viruses inside them, to prevent them infecting other cells or being shed to infect other people, so limiting the infection and minimising the damage to the infected tissues. T-cells can provide protection even when the antibodies fail to recognise the virus because they are produced in response to stable fragments of viral proteins that are less likely to differ in different variants, hence they safeguard against future mutant forms.
Neither of these is 100% effective of course and people can still become infected again and can still be infectious by shedding more viruses into the environment, but they do greatly reduce the seriousness of the infection and the risk of passing it on to other people.
However, what the researchers at the Doherty Institute, Melbourne, Australia, have shown is that unvaccinated children produce far fewer killer T-cells than adults. The researchers say this limited ability of unvaccinated children to generate strong memory killer T cell responses following natural infection may leave them vulnerable to future infections. The anti-COVID vaccines, on the other hand, are specifically designed to produce a strong T-cell response in addition to antibodies, placing vaccinated children as a significant advantage.
From the Doherty Institute press release:
Published in Immunity, the study is among the first to analyse the immune response of children following infection with SARS-CoV-2, using new technologies and a group of more than 50 children from Melbourne and Los Angeles.More information is provided in the Highlights and Summary to the team's paper published in Immunity:
They found that unvaccinated children that developed antibodies against SARS-CoV-2 also produced memory killer T cells – the cells responsible for recognising and fighting off subsequent infections, even against other variants of concern. However, these memory T cells were fewer in number in children when compared to adults.Memory killer T cells are essential for protection against severe disease in the future and while we observed these T cells in children, they were at a lower frequency compared to adults. We also found that not all household contacts who were exposed to SARS-CoV-2 generated memory T cell responses.
Dr Louise C Rowntree, co-lead author
Department of Microbiology and Immunology
University of Melbourne
And the Peter Doherty Institute for Infection and Immunity
Melbourne, Victoria, Australia.
Lead author University of Melbourne Dr Louise Rowntree, a Research Fellow at the Doherty Institute said that children’s limited ability to generate strong memory killer T cell responses following natural infection may leave them vulnerable to future infections.The killer T cells in our study target fragments of the virus that are highly stable and therefore provide protection against severe disease even when antibodies fail to recognise the variant.
Dr Carolien E. van de Sandt, co-senior author
Department of Microbiology and Immunology
University of Melbourne
And the Peter Doherty Institute for Infection and Immunity
Melbourne, Victoria, Australia
Study senior author and University of Melbourne Professor Katherine Kedzierska, Laboratory Head at the Doherty Institute said that immunity to SARS-CoV-2 infection in children is greatly understudied.It is important to continue researching how children’s immune system fights COVID-19, especially as worldwide vaccination rates in children fall far behind that of adults.
Our study makes a case for why vaccination of children should be considered a major advantage, as COVID-19 vaccines specifically aim to induce memory T cell and B cell responses. These are the key components of our immune system which protect us against subsequent SARS-CoV-2 exposures, even when new variants emerge.
Professor Katherine Kedzierska, co-senior and corresponding author
Department of Microbiology and Immunology
University of Melbourne
And the Peter Doherty Institute for Infection and Immunity
Melbourne, Victoria, Australia
The team used specific research tools called tetramers to perform in-depth immune analyses of SARS-CoV-2-specific T cells in children, which allow them to decipher several aspects of memory killer T cell responses.
Study co-senior author University of Melbourne Dr Carolien van de Sandt, a Research Fellow at the Doherty Institute, said that these killer T cells are especially important in protection against new SARS-CoV-2 variants, even those which are no longer recognised by antibodies.
Study senior author and University of Melbourne Professor Katherine Kedzierska, Laboratory Head at the Doherty Institute said that immunity to SARS-CoV-2 infection in children is greatly understudied.
The study was conducted in collaboration with the Royal Melbourne Hospital, Murdoch Children’s Research Institute, St Jude Children’s Research Hospital (USA), Children’s Hospital Los Angeles (USA) and Monash University.
HighlightsGiven this information, together with the evidence of very low risk of an adverse reaction to the vaccines, we can now say that parents who refuse to get their children vaccinated against COVID-19 are recklessly endangering them, usually because of ignorance and disinformation spread by frauds with a political agenda. It's almost like putting your children at risk of serious burns because someone told you that fireguards are dangerous and don't work.Graphical Abstract
- SARS-CoV-2-specific T cells detected ex vivo in unvaccinated seroconverted children
- Comparable spike-T cell memory responses but lower ORF1a/N-responses found in children
- Reduced clonal expansions within tetramer+ T cells seen in children compared to adults
- Prevalent Tscm phenotype and TCR motif occur in SARS-CoV-2-specific T cells in children
Summary
As establishment of SARS-CoV-2-specific T cell memory in children remains largely unexplored, we recruited convalescent COVID-19 children and adults to define their circulating memory SARS-CoV-2-specific CD4+ and CD8+ T cells prior to vaccination. We analysed epitope-specific T cells directly ex vivo using seven HLA class-I and class-II tetramers presenting SARS-CoV-2 epitopes, together with Spike-specific B cells. Unvaccinated children who seroconverted had comparable spike-specific, but lower ORF1a- and N-specific memory T cell responses compared to adults. This agreed with our TCR sequencing data showing reduced clonal expansion in children. A strong stem cell memory phenotype and common T cell receptor motifs were detected within tetramer-specific T cells in seroconverted children. Conversely, children who did not seroconvert had tetramer-specific T cells of predominantly naïve phenotypes and diverse TCRαβ repertoires. Our study demonstrates generation of SARS-CoV-2-specific T cell memory with common TCRαβ motifs in unvaccinated seroconverted children after their first virus encounter.
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