TWiV 403: It’s not easy being vaccine

The TWiV team takes on an experimental plant-based poliovirus vaccine, contradictory findings on the efficacy of Flumist, waning protection conferred by Zostavax, and a new adjuvanted subunit zoster vaccine.

You can find TWiV #403 at, or listen below.

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Attenuated influenza vaccine enhances bacterial colonization of mice

attenuated influenzaInfection with influenza virus is known to increase susceptibility to bacterial infections of the respiratory tract. In a mouse model of influenza, increased bacterial colonization was also observed after administration of an infectious, attenuated influenza virus vaccine.

Primary influenza virus infection increases colonization of the human upper and lower respiratory tract with bacteria, including Streptococcus pneumoniae and Staphylococcus aureus. Such infections may lead to complications of influenza, including pneumonia, bacteria in the blood, sinusitis, and ear infections.

One of the vaccines available to prevent influenza is an infectious, attenuated preparation called Flumist. To determine if a vaccine such as Flumist increases susceptibility to bacterial infection, the authors created their own version of the vaccine (illustrated) in which the six RNA segments encoding internal proteins were derived from the A/Puerto Rico/8/34 (H1N1) strain (allowing replication in mice), and the HA and NA proteins were derived from A/Hong Kong/1/68 (H3N2). In addition, mutations were introduced into the viral genome that are important for the safe and protective properties of Flumist. For simplicity we’ll call this virus ‘live attenuated influenza virus’, or LAIV.

Mice were inoculated intranasally with a strain of S. pneumoniae known to colonize the nasopharynx, followed 7 days later by LAIV or wild type influenza virus. Inoculation with either virus similarly increased the bacterial levels in the nasopharynx, and extended the time of colonization from 35 to 57 days. In mice that were given only bacteria and no influenza virus, the inoculated bacteria were cleared beginning 4 days after administration. The more extensive and extended colonization of virus-infected mice was not associated with overt disease.

Administration of LAIV or wild type virus 7 days before bacteria also resulted in excess bacterial growth in mice. Similar results were obtained using S. aureus. Administration of S. pneumoniae up to 28 days after virus also lead to excess bacterial growth, despite clearance of the viruses around 7 days after vaccination.

All mice died when they were vaccinated with wild type influenza virus followed 7 days later by a sublethal dose of a highly invasive strain of S. pneumoniae. In contrast, pretreatment with LAIV lead to no disease or death of any mice.

It is not known if these findings in a mouse model directly apply to humans. However, because Flumist reduces influenza virus replication, it is associated with a decrease in secondary bacterial infections. It is possible that, after administration of LAIV to humans, there is an increase in bacterial colonization of the respiratory tract. Upper respiratory tract symptoms are a known adverse effect of LAIV, and it is possible that these might be related to increased bacterial loads. It is important to emphasize that use of LAIV is not associated with severe upper or lower tract disease.

These findings are important because they show that a mouse model could be used to understand why influenza virus infection leads to increased bacterial colonization of the respiratory tract. It will be important to determine the precise mechanisms by which influenza virus infection, and the associated virus and immune-mediated alteration to the respiratory tract, allows enhanced bacterial colonization. At least one mechanism, which we discussed on episode #62 of This Week in Microbiology, involves the disruption of biofilms, allowing bacteria to enter the bloodstream.

TWiV 217: I just flu in and my arms are shot

On episode #217 of the science show This Week in Virology, Vincent, Alan, Rich, and Dickson review influenza vaccines.

You can find TWiV #217 at

Effectiveness of this season’s influenza vaccine

influenza virusThe Centers for Disease Control and Prevention has released early estimates of the effectiveness of this season’s influenza vaccine in preventing influenza infection.

Influenza vaccine effectiveness is assessed each year by the U.S. Influenza Vaccine Effectiveness Network. Patients with acute respiratory infection (ARI) are enrolled in the study; respiratory samples are taken and the presence of influenza virus is determined by polymerase chain reaction.

Data from 1,155 children and adults with ARI during December 3, 2012–January 2, 2013 were collected at five study sites and used to determine that the estimated vaccine effectiveness is 62% (95% confidence intervals = 51%–71%). This number represents the overall effectiveness of seasonal influenza vaccine for preventing laboratory-confirmed influenza virus infection associated with acute respiratory infection.

Of 1,155 children and adults with ARI, 416 (36%) were positive for influenza A or B virus. Of these, 236 (57%) were influenza A virus (all H3N2) and 180 (43%) were influenza B viruses. The immunization rate for influenza cases was 32% and 56% for individuals who did not have influenza virus. The ARI of these patients was likely caused by another agent.

It is known that this season’s influenza vaccine is a good match for the circulating viruses. Why then is vaccine effectiveness only 62%? Although the study does not distinguish between patients who received the inactivated (injected) or the infectious (intranasal) vaccine, most vaccine distributed in the US is the former. Because the inactivated vaccine is treated with formaldehyde and detergents, the viral proteins are not in their native state and do not produce the correct antibodies for optimal protection. Because the intranasal vaccine contains infectious virus, the viral proteins are unaltered and induce antibodies that are more protective. In children less than 7 years old, the intranasal vaccine provides a higher level of protection than the inactivated vaccine. It’s unfortunate that the influenza vaccine needs of the US cannot be met by current supplies of FluMist.

Based on the results of this and similar studies, some argue that it is not worth being immunized against influenza. This reasoning is faulty. Even if you are immunized and subsequently contract influenza, you are likely to be less sick than if you had not received the vaccine. According to CDC:

Influenza vaccination, even with moderate effectiveness, has been shown to reduce illness, antibiotic use, doctor visits, time lost from work, hospitalizations, and deaths.