Human Responses to Two Decavalent Rhinovims Vaccines

Abstract

Two formalin-inactivated, decavalent rhinovirus vaccines were tested in humans for acceptability and antigenicity. Infectivity titers of the vaccine antigens were low and ranged from 10(1.5) to 10(5.5) 50% tissue culture infective doses/ml. There were minimal or no side effects to either vaccine. The first inoculation of one vaccine produced antigenic responses to 30% of the administered antigens. Limited testing for heterologous antibody responses to nonvaccine antigens showed scattered responses. These findings suggest that potent multivalent rhinovirus vaccines containing antigens selected for cross-reactivity should be tested in an attempt to develop practical control measures for rhinoviruses.

Challenges in developing a cross-serotype rhinovirus vaccine

“…However, in those studies which have assessed a significant number of serotypes, crossreactivity was shown to be somewhat limited because for example only 13 of 37 tested antisera from whole virus immunised rabbits neutralised a single other virus serotype [26]. The cross-reactive virus binding and virus neutralising antibody responses in humans are also somewhat variable between individuals [12 , 27,28]. In terms of protection against virus infection, secondary infection with a heterologous virus serotype could reduce the frequency and severity of symptoms similarly to a homologous virus reinfection in one study [29], but intramuscular inactivated vaccine provided no protection against cold symptoms or virus shedding following heterologous virus challenge in another [15].…”

“…A previous attempt at this strategy with formalin inactivated decavalent whole virus preparations however demonstrated rises in neutralising antibody titres to 40% of serotypes at best [27]. A huge number of virus types would also likely need to be contained in such a vaccine because, as noted above, it has been found that large numbers of strains circulate simultaneously, with for example over 100 genetically distinct strains having been found in a small paediatric cohort in just a 2 year period [22].…”

The impact of viral genotype on pathogenesis and disease severity: respiratory syncytial virus and human rhinoviruses

“…By the late 1960s, over 50 HRV serotypes had been defined, and vaccination of volunteers did not result in heterologous neutralizing Abs. By the mid-1970s, the outlook for a HRV vaccine was dour, due the large number of serotypes, technical challenges associated with producing high valency vaccines, and poor performance of a decavalent, formalin-inactivated HRV vaccine, although the vaccine study was limited by low input titers of several HRV strains [51,52]. There is some cross-reactivity between HRV serotypes, and experimental infection of volunteers can result in protective immunity lasting at least one year [53,54].…”

50-valent inactivated rhinovirus vaccine is broadly immunogenic in rhesus macaques

“…In 1975, it was reported that two different 10-valent inactivated HRV preparations induced nAb titers to only 30-40% of the input virus types in recipient subjects 33 . However, the input titers of viruses prior to inactivation ranged from 10 1.5 to 10 5.5 TCID 50 per ml, and these were then diluted 10-fold to generate 10-valent 1.0 ml doses given i.m.…”

“…However, the input titers of viruses prior to inactivation ranged from 10 1.5 to 10 5.5 TCID 50 per ml, and these were then diluted 10-fold to generate 10-valent 1.0 ml doses given i.m. as prime and boost with no adjuvant 33 . We hypothesized that low input antigen doses are responsible for poor nAb responses to 10-valent inactivated HRV.…”