Vaccination part 8
Vaccine resistance
It’s a common observation that life finds a way.
Virions are technically not alive, but viruses (the host cell under the influence of viral genetic material) are, and, as Jeff reminds us, “life will not be contained. Life breaks free, it expands to new territories and crashes through barriers, painfully, maybe even dangerously.”
We’ve seen this with the development of antibiotic resistance, and with the development of resistance to herbicides & pesticides in agricultural practice. René Dubos, developer of gramicidin, the first commercially-manufactured antibiotic, in the 1930s, announced by 1943 that “at some unpredictable time and in some unforeseeable manner nature will strike back.” It already had; in 1940, Abraham and Chain reported that an E. colistrain was able to inactivate penicillin by producing penicillinase, and by 1942 four Staphylococcus aureus strains were found to resist the action of penicillin in hospitalized patients, with the proportion of infections caused by penicillin-resistant S. aureus increasing rapidly over the next several years, spreading quickly from hospitals to communities; by the late 1960s, more than 80 percent of both community and hospital-acquired strains of S. aureus, once universally susceptible, were penicillin-resistant. The second-generation, semisynthetic, methicillin was introduced in the 1960s, followed by rapid development of methicillin-resistant strains. Similar patterns have been seen with other bacterial pathogens involving multiple antibiotics.
Influenza A has similarly evolved resistance to the antiviral drugs amantidine and Tamiflu (oseltamivir); recently SARS-CoV-2 has evolved resistance to the antiviral drug Paxlovid (nirmatrelvir/ritonavir). Although rare, Herpes simplex virus strains have been identified with resistance to the antiviral drug acyclovir.
Might we not anticipate the same kind of eventual evasion from vaccine-induced immunity?
As one example, we might look to the pneumococcal vaccine. This represents a special case (shared with Haemophilus Influenzae), as the pneumococcus (Streptococcus pneumonia)
Is a component of the normal upper respiratory flora, and
Exists in nature in multiple (over 100 identified) serotypes
Vaccines to the pneumococcus, when first developed in the 1980s, addressed 7 serotypes, later expanded to 13 and most recently to 23 serotypes, in vaccines targeting children aged 2 months to 18 years and adults.
A result of aggressive vaccination campaigns directed both at children (ages 2-18 years) and adults (the pneumococcus is a normal inhabitant of the upper respiratory mucosa, & is involved as the most common bacterial pathogen in community-acquired pneumonia in all age groups, and in acute otitis media in children) have resulted in shifts in the circulating pneumococcus serotypes, favoring those not covered by the vaccine. The widespread use of the vaccine has served to select for vaccine-resistant strains of this genetically/serotypically-diverse bacterium colonizing our upper respiratory mucosa.
A similar phenomenon has been seen with the Haemophilus influenzae vaccine.
An epidemic outbreak of polio in 2010 in the Republic of the Congo was associated with an exceptionally high mortality rate of 47%: 210 deaths out of 445 confirmed cases; first attributed to low vaccine coverage (Polio vaccine coverage in the Congo at the time was over 70%, somewhat under the worldwide average), but later realized to be the result of the emergence of a vaccine-resistant strain involving 2 mutations in the capsid protein gene, altering the immunologic properties of the virion, providing immune escape from vaccine-induced immunity. This type of immune escape is far less likely to occur with naturally-acquired adaptive immunity, which is dependent on a broader range of immunological epitopes.
Varying degrees of vaccine resistance have been seen to emerge with vaccines targeting Streptococcus pneumoniae, Haemophilus influenzae, hepatitis B, Pertussis, Diphtheria, Neisseria meningitidis, rotavirus; and in veterinary medicine, with vaccines targeting Marek's disease, Yersinia ruckeri, avian metapneumovirus, avian influenza, avian reovirus, feline calicivirus, infectious bursal disease virus, Newcastle disease virus, and porcine circovirus type 2.
And of course we see the evolving viral antigenicity of the seasonal & pandemic Influenza viruses requiring annual redevelopment of the Influenza vaccines, and more recently of SARS-CoV-2, being played out in real time.
We might channel Jeff Goldblum (as Dr. Ian Malcolm) again:
“Gee, the lack of humility before nature that's being displayed here … staggers me.”