RSV-Why an IM Vaccine Probably Wont Help Kids Much
I have written a bit about RSV and the rush to develop vaccines
Unfortunately, based on a couple of papers on RSV it really seems that going the IM Vaccine route is not smart, and efforts to explore IVM and other repurposed drugs makes far more sense, and developing a mucosal vaccine to improve mucosal immunity makes even more sense.
This post is more about efficacy than safety although ADE is a real concern as is all the other safety concerns we saw with mRNA vaccines. Although RSV vaccines will not produce spike, there is still the concerns about lipid nano particles and immune suppression.
Anyways, from this paper I learned a few things
https://oro.open.ac.uk/67080/1/JO_PhD_Thesis_final_03102019.pdf
While prior infection can modulate disease severity, immunity to RSV infection is short-lived resulting in relatively common reinfections (Melero et al. 1997).
RSV repeatedly re-infects throughout life and re-infections can be severe (Nokes et al. 2008). Re-infection suggests an absence of sterilizing immunity to infection and disease and may in part relate to genetic diversity of the virus (Cane, Matthews and Pringle 1991; Sullender et al. 1991).
Well, thats not very promising for a vaccine since vaccine immunity is no better than natural immunity
So the question is if we are all being repeatedly being reinfected throughout life why is this infection more serious in young children/infants
It often comes down to the basics of anatomy….Babies are born with the tiniest of airways. Viruses like RSV inflame those airways, making it difficult to breathe. The smaller the airway, the less inflammation it takes to close it
That makes some sense. So as Children get older their airways increase in size. Even though they still get reinfected, its not their immunity that comes from previous infection that’s responsible for less severe symptoms , its the fact they have bigger airways.
I found another paper that focuses more on immunology
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5355638/
Natural infection results in incomplete immunity, permitting recurrent infection in childhood as well as infections in adults, including the elderly.
Thats confirming what the other paper said
Absolute T-cell counts during RSV infection are inversely associated with age; thus, T-cell lymphopenia is more pronounced in younger patients . Children with more severe illness and those requiring ventilation have reduced circulating T-cell counts (all subsets) compared to those with less severe infection, and in lung tissue from fatal cases, CD4+ and CD8+ T cells are sparse .
Thats somewhat concerning in the COVID Vaccine since there are papers suggesting the vaccines are immunosuppressive and may transiently reduce T-Cell levels. You probably don’t want to be vaccinating kids during periods that RSV likes to spread. This might explain the increased severity of RSV infections if such reports are true
In experimental infections, nasal RSV IgA appears to confer more protection than serum neutralizing antibody, and the response may be more durable. Similarly, in infants and children with natural infection, it is the development of the IgA response that appears to correlate with recovery .
That supports the argument for mucosal vaccines rather than IM Vaccines
During convalescence, circulating RSV IgG- but not IgA-producing memory B cells are present, in contrast to the case for natural influenza virus infection, where influenza virus IgA-producing memory B cells are detectable . Overall, a possible deficit in IgA memory, especially in childhood, when IgA appears to offer important protective immunity, may contribute to recurrent infections .
Interesting
In contrast, in elderly patients it is a deficit in circulating serum neutralizing antibodies that appears to predispose to RSV disease .
This suggests IM RSV Vaccines might be helpful in the Elderly, if they can put to bed the safety concerns