Coinfection in the host can result in functional complementation between live vaccines and virulent virus

Abstract

One of the greatest achievements of the last century is the development of vaccines against viral diseases. Vaccines are essential for battling infectious diseases and many different formulations are available, including live attenuated vaccines. However, the use of live attenuated vaccines has the potential for adverse effects, including reversion of pathogenicity, recombination, and functional complementation in the host. Marek’s disease is a serious disease in poultry controlled by live attenuated vaccines that has resulted in increased virulence over the decades. Recombination between circulating field viruses or vaccines is a proposed mechanism for the increase in virulence, however, complementation between vaccines and field strains has not been demonstrated in chickens. Here, we describe functional complementation of vaccines with virulent virus to functionally complement transmission and spread in the host. Using the natural virus-host model of Marek’s disease in chickens, our results show dual infection of target cells in chickens with vaccine and virulent virus providing the opportunity for recombination or complementation to transpire. Interestingly, our controlled results showed no evidence of recombination between vaccine and virulent virus, but functional complementation occurred in two independent experiments providing proof for complementation during natural infection in vaccinated individuals. These results suggest complementation as a potential mechanism for vaccine-mediated viral evolution and the potential for complementation should be taken into consideration when developing novel vaccines.

Comparative Analysis of Multiple Consensus Genomes of the Same Strain of Marek’s Disease Virus Reveals Intrastrain Variation

“…Secondly, the 16 unique SNPs in US of CVI988 GenBank.BAC impacting US2, US3, SORF4 and US6 / gD have been proposed as evidence of naturally occurring recombination between CVI988 and virulent strains (63). To date, a total of seven isolates from China have been described as natural recombinants of CVI988, largely on the basis of these 16 SNPs (64)(65)(66). The two new consensus genomes of CVI988 generated as part of this study share the same nucleotides in all 16 positions with these isolates, calling into question whether they are in fact natural recombinants of CVI988.…”

“…The copyright holder for this preprint this version posted September 4, 2023. ; https://doi.org/10.1101/2023.09.04.556264 doi: bioRxiv preprint US6 / gD have been used as the main evidence of naturally occurring recombination between CVI988 and virulent strains, starting in 2018 by He et al (59). Multiple studies have followed, resulting in a total of seven isolates from China being described as natural recombinants of CVI988 on the basis of these 16 SNPs (60)(61)(62). Our two new consensus genomes of CVI988 share the same nucleotides in all 16 positions with these seven isolates, implying that they are likely to be field isolates of CVI988 and not natural recombinants as previously described.…”

Immune escape of avian oncogenic Marek’s disease herpesvirus and antagonistic host immune responses

“…Complementation is another adverse mechanism associated with MD vaccines. Using natural coinfection models, the MD vaccine and MDV have been shown to infect the same cells in vivo, resulting in functional complementation, and the nontransmissible MDV was transmitted to chickens via one round of transmission 118 .…”

Mosaic Recombination Inflicted Various SARS-CoV-2 Lineages to Emerge into Novel Virus Variants: a Review Update

“…A recombinant SARS-CoV-2 is a variant evolved by the combination of genomes of at- least two different parent lineages. Natural recombination occurs when a minimum of two variant genomes co-infect the same host cell simultaneously and interchange their genetic material[ 22 ]. The evolutionary causes to the incidence of recombination, especially RNA viruses, are not as much clear due to huge population sizes and enormous mutation occurrences [ 23 ].…”