Recombinant Viral Vector Vaccines

Summary

Over the last decennia different recombinant viral vector vaccines for poultry have been introduced in several countries.

The first vaccines were all based on the Fowl pox(FP) virus used as the vector (e.g. the avian influenza (AI) recombinant (r) FP/H5, NewcastleDisease (ND) rFP/ND, infectiouslaryngotrachetis (ILT) rFP/ILT vaccines. The most recent ("second generation") viral vector vaccines introduced are based onthe herpes virusofturkeys(HVT) vector like the recombinant(r) HVT/(ND), rHVT/ILT, rHVT/Infectious Bursal Disease (IBD) and the rHVT/H5(AI) vaccines.

These novel vaccines in particular the rHVT vector vaccines have shown to be of an economic benefit for the poultry industry compared with the conventional vaccines. However failures due to several issues inherent on these vaccines have been observed. The different issues and its control to prevent those failures will be discussed.

Key words: recombinant viral vectored vaccines, fowl pox virus ,herpesvirus of turkeys.

The first generation of recombinant viral vector vaccines based on the FP vector like the rFP/ILT showed applied at 8-10 weeks by the wingweb route an improvement in the control of ILT compared with the conventional live ILT vaccines.

However the disadvantages of the FP vector vaccines are the rather short duration of protection in long lived birds in contrast to the "live long" protection obtained with the HVT vector vaccines(8,9) due to the persistent nature of the HVT vector.In addition FP virus maternal antibodies (Mab) may interfere with the onset of immunity in chickens vaccinated at an early age and a "no take" of the FP vector vaccine will occur in birds previously vaccinated or infected with FP. Other question of concern is the safety of the FP vector vaccines administrated in ovo (15)

Most of the FP virus vector vaccines will be over time replaced by the much more advantageous HVT vector vaccines.

The rHVT/ND,ILT and IBDV vector vaccines have clearly shown to be efficacious, improving the performance of the vaccinated flocks, consequently providing economical benefits to the poultry industry compared with the conventional live ND,ILT and IBD and inactivated ND vaccines used to control respectively ND or ILT or IBDV.(4,6,11,12,14).

Several issues inherent on these vaccines have shown specifically under field conditions to play a role in the failures of the efficacy of these novel vaccines.(5) Although most of these issues can easily be prevented to avoid these type of failures.

With the focus on the rHVT vector vaccines the isssues and how prevent these issues will be in detail discussed in this presentation:

Application/Administration

The rHVT vector vaccines are like the HVT vaccines applied subcutaneously at one day of age or administrated in ovo in the hatchery. The rHVT vector (similar as the HVT vaccines) does not spread,any non vaccinated/missed chicken will not be protected. Even in the case of very small number of "missers" in an endemic area a negative effect on the efficacy can be observed.(5,17).

Particular in highly endemic areas, any errors in the subcutaneous application at one day of age or the in ovo administration plays an important role in failing to provide optimal protection.

Proper application is one of the main important issue in the success of these novel vaccines.

Onset of Immunity

Complete protection(>90%) against the expressed ed foreign gene antigens of the rHVT vector vaccines is not achieved untill approximately 3-4 weeks of age.

High uniform Mabs in for NDV in rHVT/ND and for IBDV in rHVT/IBD vaccinated birds have shown to minimize the effect of the delay in onset of immunity (4,11)

In (v)ND endemic locations a live safe conventional ND vaccine is recommended at one day of age to provide the early protection for ND.(4,12,13,14)

Protection against MD

It has been shown that with the rHVT vector constructs the level of protection against MDV may be compromised in comparison with the parent strain in the case of virulent Marek''''s Disease virus(MDV) exposure at an early age.(MDV shedder trials).Combining the rHVT vector vaccines with the serotype1MDV CVI988 (Rispens strain) or serotype 2 MDV SB1 same level of protection has been observed in comparison with HVT+CVI988 or HVT+SB1.(3,6)

Compatibility rHVT vector vaccines and with other MDV vaccines

Simultaneously vaccinating or combining different rHVT vector vaccines will result in the interference of expressing the ed foreign gene antigen of one of the rHVT vector vaccines.This interference is most likely expressed as an extended delay of the onset of immunity of one of the combined rHVT vector vaccines.

Combining rHVT vector vaccines with conventional HVT vaccines to improve e.g. MD protection will have a serious negative effect on the efficacy of the rHVT vector vaccine(2,16)

Persistence and possible transmission of the challenged virulent virus in rHVT vector post challenged vaccinated birds

In laboratory trials chickens vaccinated in ovo or by the subcutaneous route at one day of age with the rHVT/ILT and challenged at 4-5 weeks of age no reduction of the replication of the challenge virus in the upper respiratory tract for a short period of time even in birds without any clinical symptoms was observed.(1,6,9).In vNDV challenged birds simultaneously vaccinated with the rHVT/ND and a live ND vaccine a significantly reduction of the challenge virus dose in the trachea was observed in contrast to the birds vaccinated with the recombinant alone (12)

However the transmission of the challenge virus to susceptible birds has yet not been shown.(Rosenberger pers.comm.2011)

Additional issues not specific related to the rHVT vaccines are immunosupprsion , chick quality etc

Conclusion

The success of these novel rHVTviral vector vaccines largely depends on:

a) Proper application of the recombinant HVT viral vector vaccines by the subcutaneous route at one day of age or by the in ovo administration.

b) High uniform NDV and IBDV Mabs derived from properly vaccinated parent stock will reduce the effect of the delay in the onset of complete protection in chickens vaccinated with the rHVT/ND or rHVT/IBDV vector vaccines. In addition in vND endemic areas a live ND vaccination at one day of age is required.

c) Combining the rHVT viral vector vaccines with MDV SB1 or CVI988 vaccine in high risk MDV areas.

d) Avoid combining different recombinant viral vector vaccines or simultaneously vaccination with any conventional live vaccine not recommended by the manufactory.

References

1.Garcia,M.,G Zavala,A.Vagnozzi,S.M.Riblet and A.Mundt.Evaluation of the protection induced by commercial available fowl poxvirus(FPV) and herpesvirus of turkey HVT viral vector vaccines against infectious laryngotracheitis(ILT) in broilers. Proc.1^st International Avian Resp. Dis.Conf. Athens USA 42 2011

2.Godoy,A.,M.Esaki,P.Flegg,J.Rosenberger,S.Rosenberger,K.M.DorseyandY.Gardin. Compatibility of vectored LT vaccines and Vectormune HVT NDV. AAAP Conf.St Louis 2011

3.Hein,R.G. and G.Slacum.Efficacy against Very Virulent(vv) Marek''''s Disease Virus (MDV) of the HVT/ND Recombinant (Innovax-ND-SB) and the Immunity against Virulent(v)Newcastle Disease Virus(NDV). Proc. 56th Western Poultry Dis. Conf Las Vegas USA 83 2007

4Hein,R.G.,J.F.Rios,A.Aguilera and J.Domhof.Newcastle Disease(ND) Efficacy in Broilers Vaccinated at One Day of Age with the Recombinant HVT/F(ND):INNOVAX-ND-SB

Challenged with the Mexican vND virus isolate Chimalhuacan.Proc.75^th Western Poultry Dis.Conf.Puerto Vallarta Mexico pg32-33 2008.

5.Hein,R.,G.Slacum,P.Lynch and K.Honegger.Recombinant HVT/ILTV Vaccine(INNOVAX-ILT) Field Application Issues Proc.43^rd. Nat.Meeting on Poultry Health and Processing Ocean City Md.73 2008.

6.Hein,R.,Novel HVT/ILT Recombinant Vaccine to Simultaneously Control Infectious Laryngotracheitis and Marek''''s Disease in Chickens(INNOVAX-ILT).Proc.VI Int.Symposium on Avian Corona and Pneumoviruses Rauschholzhausen Germany 385-386 2009

7.Johnson,D.,A.Vagnozzi,F.Dorea,S.M.Riblet,A.Mundt,G.Zavalla. Protection Against Infectious Laryngotracheitis by In Ovo Vaccination with Commercially Available Viral Vector Recombinant Vaccines. Avian Dis.54:1251-1259,2010.

8.Melson,L and K.Jensen, Duration of Immunity in Chickens Following Vaccination with a Recombinant Herpesvirus of Turkeys Vaccine Expressing the Fusion(F) Antigen of Newcastle Disease Virus. Proc.1^st International Avian Resp. Dis.Conf. Athens USA 59 2011

9.Melson,L and K. Jensen, Duration of Immunity in Chickens Following Vaccination with a Recombinant Herpesvirus of Turkeys Vaccine Expressing Infectious Laryngotracheitis Antigens. Proc.1^st International Avian Resp. Dis .Conf. Athens USA 65 2011.

10.Morgan,R.W.,J.Gelb,C.S.Schreurs,D.Lutticken,J.Rosenberger, P.J.Sondermeijer .Protection of Chickens from Newcastle and Marek''''s Disease with Recombinant Herpesvirus of Turkeys Vaccine Expressing the Newcastle Disease Virus Fusion Protein. Avian Dis.36: 858-870 1992.

11.Le Gros,F.X.IBD Efficacy data in presence of Maternal Antibodies in Broilers and Layers with a Novel Vector HVT-IBD vaccine. Proc.VI Int. Symposium on Avian Corona and Pneumoviruses Rauschholzhausen Germany 376-384 2009

12.Palya,V.,Z.Penzes,T.Horvath,V.Kardi,K.Moore and Y.Gardin. Comparative Efficacy of Several Vaccination Programs including or not including Recombinant HVT-ND Vaccine against Challenge with Mexican Chimahuacan NDV strain. Proc.75^th Western Poultry Dis.Conf.Puerto Vallarta Mexico pg36-38 2008.

13.Rauw,F.,YGardin,V.Palya,S.Anbari,S.Lemaire,M.Boschmans,T.v.d.Berg and B.Lambrecht.

Improved vaccination against Newcastle disease by an in ovo recombinant HVT-ND combined with an adjuvanted live vaccine at day old. Vaccine vol. 28 823-833 2010.

14.RiosJ.F. and R.G.Hein. Field Evaluation of a Recombinant rHVT/NDV vaccine in Broilers in a vNDV Region in Mexico.Proc .Western Poultry Dis. Conf. Vancouver Canada pg32-34 2010.

15.Rosenberger,J.K.andS.C. Rosenberger ,ILT Vaccines Field and Laboratory Assessments.

Proc.41^st Nat. Meeting on Poultry Health and Processing Ocean City Md.81-85 2006.

16.Slacum,G.,R.G.Hein and P.Lynch The Compatibility of Recombinant HVT vaccines and other MD vaccines .Proc. 76^th Western Poultry Dis.Conf.Sacramento 2009.

17.Williams,C.J. and B.A. Hopkins,field evaluation of the accuracy of vaccine deposition by two different commercially available in ovo injection systems.Poultry Science 90.223-226 2011

This paper was presented at the XVII World Veterinary Poultry Association (WVPA) Congress in Cancún, Mexico, August 14-18, 2011. Engormix.com thanks the author and the organizing committee for this huge contribution.