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We thank Andrew Rycroft and colleagues for highlighting areas of our approach that require further explanation.
First, we must clarify that we did not suggest oral administration of a vaccine produced using Pasteurella multocida. Our speculation that a vaccine may block virus receptor sites in the intestine referred to an oral vaccine using live transformed Lactobacillus acidophilus.
Regarding the transformability of P multocida, this bacterial species is naturally competent and displays a high frequency of DNA uptake sequences.1 We do not have an explanation for how viral RNA is converted to DNA during the transformation process, but our method has been successfully applied in the development of recombinant vaccines for several RNA viruses (including infectious bronchitis virus, infectious bursal disease virus, classical swine fever virus, foot-and-mouth disease virus type O and rabies lyssavirus) produced and used in Myanmar between 1994 and 2006.
P multocida transformed using this method are very stable and can be stored as freeze-dried seed cultures, so there is no problem with batch-to-batch variation. The concentration of formalin used to inactivate the bacteria will also further stabilise the viral antigens they express.
The viral antigens expressed by transformed P multocida are predominantly verified using slide agglutination of bacterial cells or agar gel precipitin testing of bacterial lysates with specific antisera. As glutaraldehyde treated erythrocytes incorporating serum antibodies on their surface are used, P multocida expressing the corresponding viral antigens will bind with these antibodies and become linked to the erythrocytes. Passive haemagglutination is, therefore, unlikely to be a confounding factor.
Furthermore, the expression of rabies lyssavirus glycoprotein by transformed P multocida was recently confirmed by western blot at the Department of Medical Research in Myanmar. It has also been confirmed that P multocida transformed with porcine reproductive and respiratory syndrome virus (PRRSV) contains a gene segment that encodes the PRRSV nucleocapsid protein. The sequence of this gene segment has been deposited in GenBank (accession number MT411898) and will be available online shortly.
The field vaccination of 9000 birds that we discussed previously (VR, 4/11 April 2020, vol 186, p 419) was a response to an immediate clinical problem and not an experiment. As such, there were no control groups with which to compare the vaccinated birds. However, the safety and efficacy of the IBV vaccine produced using our method had already been established.2
As we pointed out previously, the evidence for this IBV vaccine being of value in the treatment of poultry in Myanmar is empirical, but it is independent and consistent over the past 25 years. However, we reiterate that any new vaccine produced using this method would need to be fully tested for safety and efficacy before being adopted for widespread use.
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