IMMUNOGLOBULINS FOR NON-SURGICAL STERILIZATION OF DOMESTIC CATS - - PowerPoint PPT Presentation

▶
immunoglobulins for
SMART_READER_LITE
LIVE PREVIEW

IMMUNOGLOBULINS FOR NON-SURGICAL STERILIZATION OF DOMESTIC CATS - - PowerPoint PPT Presentation

Nov 19, 2023 10 likes •245 views

AAV-VECTORED GENERATION OF GNRH-BINDING IMMUNOGLOBULINS FOR NON-SURGICAL STERILIZATION OF DOMESTIC CATS Lindsey Marie Vansandt, Danijela Markovic, Marlene L. Biller, Jackie Newsom, Helen Bateman, William F. Swanson, Bruce A. Hay

slide-1
SLIDE 1

AAV-VECTORED GENERATION OF GNRH-BINDING IMMUNOGLOBULINS FOR NON-SURGICAL STERILIZATION OF DOMESTIC CATS

Lindsey Marie Vansandt, Danijela Markovic, Marlene L. Biller, Jackie Newsom, Helen Bateman, William F. Swanson, Bruce A. Hay

slide-2
SLIDE 2

Non-surgical sterilization of domestic cats

 80 million free-roaming cats in the

United States

 2.7 million shelter dogs and cats are

euthanized each year

 Outdoor cats have negative impacts on birds

and other wildlife species

 Surgical sterilization common

approach

 $, labor-intensive, highly-technical

 Non-surgical sterilization more

field-friendly

slide-3
SLIDE 3

Gonadotropin Releasing Hormone (GnRH)

 Master regulator of reproduction

slide-4
SLIDE 4

Gonadotropin Releasing Hormone (GnRH)

 Master regulator of reproduction  Targeted with immunocontraceptives

slide-5
SLIDE 5

Immune system

slide-6
SLIDE 6

Muscle cells

slide-7
SLIDE 7

Cat GnRH antibody DNA Cat GnRH antibody protein

Adeno-associated virus (AAV) vector

slide-8
SLIDE 8

Vectored contraception

 Determined sequence of anti-GnRH monoclonal

antibody SMI41

 Introduced into an AAV2/8 vector

slide-9
SLIDE 9

Vectored contraception

 Determined sequence of anti-GnRH monoclonal

antibody SMI41

 Introduced into an AAV2/8 vector

OBJECTIVE: To determine if AAV2/8 vectored expression of SMI41 could induce long-term infertility in the domestic cat (Felis silvestris catus)

slide-10
SLIDE 10

(n = 3)

Study design

Pre-Tx (4 mo) (n = 3) 3.4x1013 viral particles Tx (Days 7 – 30) Post-Tx (Months 1-6) D M M M M M W M W

slide-11
SLIDE 11

(n = 3)

Study design

Pre-Tx (4 mo) (n = 3) 3.4x1013 viral particles Tx (Days 7 – 30) Post-Tx (Months 1-6) D M M M M M W M W

No injection site reactions, adverse events,

  • r
  • ff-target

effects observed

slide-12
SLIDE 12

SMI41 antibody production

slide-13
SLIDE 13

SMI41 antibody production

In the mouse, threshold titer level to produce infertility was 200 µg/ml

slide-14
SLIDE 14

Hormone profiles

Pre-Tx Tx Post-Tx

slide-15
SLIDE 15

Hormone profiles

Pre-Tx Tx Post-Tx

slide-16
SLIDE 16

Hormone profiles

Pre-Tx Tx Post-Tx

slide-17
SLIDE 17

Hormone profiles

P=0.4065 P=0.0914

slide-18
SLIDE 18

Anti-SMI41 antibody production

2000 4000 6000 8000 10000 12000 14000 16000 18000 20000 0 day 1 day 2 day 3 day 4 day 5 day 7 day 14 day 21 day 28 day 60 day 90 day

  • Fl. units

Anti-cSmI41

slide-19
SLIDE 19

Anti-SMI41 antibody production

2000 4000 6000 8000 10000 12000 14000 16000 18000 20000 0 day 1 day 2 day 3 day 4 day 5 day 7 day 14 day 21 day 28 day 60 day 90 day

  • Fl. units

Anti-cSmI41

slide-20
SLIDE 20

Conclusions

 Expressed a functional GnRH antibody in the cat

using a recombinant AAV-vectored approach

 Suspected immunogenicity prevented the threshold

titler level to inhibit ovarian cyclicity to be achieved

slide-21
SLIDE 21

Acknowledgements

slide-22
SLIDE 22

TEAM CAT

slide-23
SLIDE 23

QUESTIONS?