Immunosignatures can predict vaccine efficacy paper 02-28-2014d1558

2015-01-13

Immunosignatures can predict vaccine efficacy paper 02-28-2014d1558

http://www.pnas.org/content/110/46/18614.short
"C:\Users\kurtw_000\Box Sync\DocDR\2013\12-11-2013d0915\Immunosignatures can predict vaccine efficacy.pdf"
paper by Bart

By using

a mouse in?uenza infection, we show that the immunosignaturing
of a natural infection can be used to discriminate a protective from
nonprotective vaccine.

Further, we demonstrate that an immuno-

signature can determine which mice receiving the same vaccine
will survive.

Finally, we show that the peptides comprising the

correlate signatures of protection can be used to identify possible
epitopes in the in?uenza virus proteome that are correlates
of protection.

data reported in this paper have been de-

posited in the Gene Expression Omnibus (GEO) database,

Correlates of protection are immune responses that are speci ? c

products of the vaccine and statistically associated with pro-
tection

Here we eval-

uate whether immunosignatures can characterize and stratify
vaccines into those that are ef ? cacious and those that are not.

On a ? ner scale, individual

monoclonal antibodies bind to a surprisingly large number of random-sequence peptides and are detectable within a complex
mixture of competing antibodies (7, 12)

in?uenza model, A/PR/

8/34

study plan: 5 groups of 10 female BALB/c mice were immunized. Challenged with H1N1 A/PR/8/34 (PR8 virus). 3 groups vaccinated with inactivated viruses: killed PR8 and the two seasonal vaccines: A/Wisconsin/67/2005 (H3N2) and B/

Malaysia/2506/2004. Mock vaccination group. 5th group vaccinated a single time with a sublethal dose of live PR8 virus

The two seasonal vaccines were partially protective, re-

sulting in 60% and 80% survival.

Live and Inactive In?uenza Immunizations Produce Different Immu-

nosignatures

The Immunosignature Can Distinguish Closely Related Vaccines
The Immunosignature of a Known Protective Response Can Predict

Outcome Following Challenge

-SAM algorithm uses a permuted t-test
Seasonal Vaccine Recipients Have Distinct Immunosignatures, Which

Correlate with Outcome Following PR8 Challenge

-Hamming distance
The Immunosignature Can Be Bioinformatically Tracked Back to the

Epitopes on the A/PR/8/34 Proteins.

To extend the analysis of potential correlates of protection, an

informatics analysis of the 94 peptides distinguishing the sur-
viving and nonsurviving mice from each other was conducted.
Thirty-eight of these peptides that were increasingly recognized
in the survivors vs. those that died.

Systems vaccinology
Apart from vaccine development, the ability to predict whether

an individual would survive a lethal infection may have appli-
cation in the public health response to pandemic disease