Re: protection of several old H1-vaccines in mice
11 vaccines examined (only HA ?) <1950 better
escape mutants map to site sa
=== page 2: 9:41
H1N1 viruses used in this study are as follows:
A/Swine/Iowa/30 (Sw/30)
A/Puerto Rico/8/34 -MSSM (PR8)
A/Weiss/43 (Wei/43)
A/New Jersey/8/1976 (NJ/76)
A/USSR/92/77 (USSR/77)
A/Houston/20593/84 (Hou/84)
A/Texas/36/1991 (Tx/91)
A/Brisbane/59/2007 (Bris/59/07)
A/California/04/2009 (Cal/09)
A/Netherlands/602/2009 (Neth/09)
A/Northern Territory/60/1968 (NT/68)
A/Brisbane/10/2007 (Bris/10/07)
as H3N2 controls
Cal09 6:2 : HA and CA from Cal/09 , rest from PR8
6B9 : 1918, IgG2a
39E4 : 1918 , IgG2a
29E3 : Cal/09 , IgG2b
=== page 3 , 9:53
2*15myg of inactivated virus or 1918 VLP 14 days apart "vaccination" (=active immunization ?)
150 myg monoclonal antibodies(mAbs) 6B9,39E4 - , 29E3 "passive immunization"
Cal/09 : markedly , 5e4pfu, 22.5% weight loss ("wl") by day 8
Bris/59/07 : fewer
Neth/09 , 5e4pfu,C57B/6, more wl than with Cal/09
Cal/09,Neth/09(21d,1e3pfu) all survived
Cal/09,Neth/09(21d,5e4pfu) few wl
=== page 4 , 10:17
brb 7min
figure 1
what's "mock" "in contrast, mice previously mock-infected succumbed ...")
mock = placebo ?
no vax,Neth/09 : "endpoint" by day5
Cal/09 6:2,Neth/09 : no deaths, modest wl,no virus in lungs
SW/30,Neth/09 : no deaths , no virus in lungs on day 6, wl=18.2%
NJ/76,Neth/09 : no deaths , no virus in lungs on day 6 , wl=18.2%
Wei/4,Neth/09 : no deaths , high virus in lungs on day 6 , wl >18.2%
1918 VLP,Neth/09 : no deaths, wl similar to {Cal/09 6:2,Neth/09}, no virus in lungs on day 6
USSR/77,Neth/09 : ~40% deaths, extensive wl, titers on day 6 lower as no vax,Neth/09
Hou/84,Neth/09 : similar
Tx/91,Neth/09 : similar
Bris/59/07,Neth/09 : similar
=== page 5 , 10:55
graphs ...
wl and survival strongly depends on initial dose (limit ~5e4pfu)
NT/68 protects a bit, reason unclear
"inactivated vaccines" , I still don't know whether this is whole-virus or only HA or HA+NA
table1, #mouse titers induced by vaccination
cross reactive neutralizing antibodies , I don't fully understand this , skip that part
reason for protection are the epitopes (--> humoral ?)
150mAbs -24h,
=== page 6 , 11:13
graphs...
ahh, why do we need text, when we have graphs
A:wl by day 5 from Neth/09 infection,C57B/6,2*15myg,(14d,14),8e5pfu {do we get that much by breathing ?}
Code:
wl by day 5 in %
% survival by day 5
10*(log(titers in lungs by day 3))
10*(log(titers in lungs by day 6))
10*log(titers from mAbs showing expected protection from CA/09 challenge)
----------------------------------------------------------------------------
04 99 -- -- mock
22 20 65 46 07 USSR/77
22 25 62 36 07 NT/68
22 -- 61 38 07 Hou/84
22 60 60 16 07 Tx/91
22 40 63 40 07 Bris/59/07
24 00 -- -- Bris/10/07
12 99 -- -- 34 Cal/09 6:2
12 99 48 -- 22 1918 VLP
17 99 44 -- 19 Sw/30
17 99 50 -- 16 NJ/76
21 99 65 41 07 Wei/43
27 00 69 55 07 no vax(control)
-- -- -- -- 28 Neth/09
27 00 66 59 07 control mAb
-2 99 38 47 24 29E3(Cal/09)
01 99 52 51 -- 6B9(1918)
06 99 43 56 21 39E4(1918)
13 99 49 31 -- Poly(Cal/09)
-- -- -- -- 16 Cal/09 virus
{I think, this table will be central in my -hopefully better- summary}
brb 6min
specific : 110 titers
polyclonal: 40 titers
results from antibody treatment is hopefully shown later in a similar table, so it can
just be added here. So I skip this part
=== page 7 , 12:22
table 2
I never know in these tables what's horizontal and what vertical
I want protection against potential Cal/09 infection and I take row 10 to measure this
and include it in my above table
escape mutants CA/09 6:2
mAbs 6B9,39E4, (1918-specific) G172E,K171E,
29E3(******-specific) K171E,K171Q,K180N
brb 5min
table 3 HI activity of mAbs {without escape mutants ?}
Discussion:
----------------
starts as "abstract" or "introduction"
table 4: in vivo titers
(integrate in above table)
Code:
activity against Cal/09 6:2 (*100 minimal myg/ml)
activity against Bris/59/07 (*100 minimal myg/ml)
activity against 1918VLP (*100 minimal myg/ml)
10*log(HI-titers in vivo)
name of antibody
---------------------------------------------
15 99 15 -- 1918HA 6B9
15 99 15 21 1918HA 39E4
04 99 08 24 Cal/09 HA 29E3
99 99 -- 07 Nipah W ----
-- -- -- 16 Cal/09 virus
=== page 8 , 13:08
figure 4 (include in above table)
inactivated vaccines induce humoral and minimal cellular immunity
they think that their findinds for mice will be similar in humans
=== page 9 , 13:27
nucleotide differences CA/09 -- Neth/09 :
CA/09: A1218G(1),T1872C(1),G1758A(2),T670C(3),G1986T(3),
T298C(4),C622A(4),G640A(4),G891A(4),A972G(4),G1012A(4),A1044G(6)
Neth/09:T2023C(1),A1741C(3),C1118T(5),A322G(6),A408G(6),A945C(6),G1219A(6)
amino acid differences CA/09 -- Neth/09 :
CA/09: S224P(3),S100P(4),L208I(4),A214T(4),V338I(4)
Neth/09: M581L(3),T373I(5),I108V(6),V407I(6)
figure 5, mutations of the involved viruses at the antigenic sites in HA
List: (later...)
Cb(78-83)
Sa(128-129,156-160,162-167)
Sb(187-198)
Ca1(169-173,206-208,238-240
Ca2(140-145,224-226)
H3-numbering , Brownlee+Fodor (2001)
=== page 10 , 13:43
3d-picture of HAs
however the yellow escape mutation positions are identical in 1918 and 2009
=== page 11 , 13:47
make a more complete table of antigenic sites of ~50 viruses , human and swine, 1918-2009 (later)
thinks protection from cell-based immunity and NA play a minor rule
good protection by Tx/91 is unexplained (I remember that that particular strain caused
some GB)
what's monoclonal,polyclonal ?
1976 - why do we have no estimates, how many % of ******-infected people had had
the 1976 vax ? (just ask them !)
the protection back to 1943, does it also hold for the 1977-semi-pandemic , which also
mainly infected children ?
so longterm protection (1943 back to 1918 up to 2009 = 116 years
yet the seasonal vaccine is often a bad match (why ?)
H1N1 antigenically frozen in pigs ? -----edit----- yes, see e.g. the antigenic site Sb in the table below
=== page 12 , 14:08
possible future pandemics from frozen viruses {but we can prepare with vaccine}
same study in humans ? ******=CA/09 is not lethal, usually mild, most people will be infected
earlier or later anyway. In USA, where this site is located, they even have death-penalty,
so you could use these people. However, not in the same country since else the judges might
be more willing to speak death penalties. It all depends on _how many_ such experiments
in humans you wanted to do. Probably not reasonable in this case, but when we get
a severe H5N1-pandemic it could be important.
First verify some few of the results in ferrets or swine
brb 3min
=== page 13 , 14:23
references not read
~4.5 hours in total , 2 tables still to be made , the central table still to be studied and
the results comprehended,learned,visualized
---------------------------------------------------------------------------------------
the tables are not near the referring text
the whole paper writing process is ineffective, you need to long to rea it and the abstract
and author summary is not informative enough (IMO)
Why these long papers and no shorter presentations ?
In math you skip the proofs and just read the theorems for a first understanding,
what are the theorems here ?
it took 9 months, too late for wave 1,wave 2,(wave 3 in Mex.)
pdf , no data are given , so I had to estimate the values for my central table
from graphs.
Data would be useful so we can make our own tables, own graphs ,
maybe better presented. I assume this is not in the interest of the authors and that's
why data and computer-readable tables and plain text (easy to quote and discuss in forums)
are usually not provided (?)
