Influenza A virus — Questions

Strain selection. Twice a year the World Health Organization reviews surveillance data and recommends the strains for the coming season.

Egg-based production. The vaccine virus is grown in embryonated hen eggs. Because wild strains often grow poorly, a high-yield reassortant is made by combining the surface genes (haemagglutinin and neuraminidase) of the recommended strain with the internal genes of a laboratory strain that grows well in eggs. The harvested virus is then inactivated and, for most products, split.

The problem. Growth in eggs is slow, limiting how quickly the vaccine can be updated, and the virus can acquire egg-adaptation mutations in haemagglutinin that change the antigen so the vaccine matches the circulating strain less well. Cell-based and recombinant production avoid egg adaptation.

• (a) False. Inactivated influenza vaccine is recommended, not contraindicated, in pregnancy and in HIV at any CD4 count; it is non-live and safe, and both pregnancy and HIV raise the risk of severe influenza.
• (b) True. HPV vaccination is recommended for HIV-infected people regardless of CD4 count, ART use or viral load, including men who have sex with men up to about 40 years, because of their high HPV-associated cancer risk.
• (c) True. Hepatitis A vaccine is inactivated and safe in HIV; the standard two-dose schedule is appropriate, and chronic liver disease is itself an indication. Checking post-vaccination antibody is reasonable, as the response may be reduced.
• (d) False. The varicella vaccine is live and contraindicated at a CD4 count of 150 cells/uL. Give varicella-zoster immunoglobulin (VZIG) for post-exposure prophylaxis instead.

• Pfizer-BioNTech COVID-19 vaccine (Comirnaty): mRNA vaccine in a lipid nanoparticle, encoding the pre-fusion spike protein.
• Cervarix: virus-like particle (HPV L1) vaccine, bivalent (types 16 and 18), with the AS04 adjuvant.
• Annual inactivated influenza vaccine: inactivated (killed) vaccine, usually split or subunit, grown in eggs or cell culture.
• Mumps vaccine: live attenuated vaccine (the Jeryl Lynn strain), given within MMR.
• Shingrix: recombinant protein subunit vaccine (varicella-zoster glycoprotein E) with the AS01B adjuvant.

Nature. A cold-adapted, live attenuated influenza vaccine given intranasally. The vaccine strains replicate at the cooler temperature of the nose but not in the warmer lower respiratory tract, so they induce local immunity without causing disease.

Advantage. Being live and mucosal, it raises secretory IgA at the portal of entry and a broad response, and the needle-free route suits children.

Composition. Reformulated each year by reassortment to carry the recommended seasonal haemagglutinin and neuraminidase on the cold-adapted backbone.

Limitations. As a live vaccine it is contraindicated in pregnancy and in immunocompromise, and it is used in a defined age range rather than across all groups; inactivated vaccine is used where a live product is unsuitable.

A complete answer lists the priority groups, gives the rationale, and critiques the strategy.

Priority groups. Pregnant women; people living with HIV; those with chronic cardiac, pulmonary, renal or metabolic disease; the elderly; and healthcare workers. The very young are also at higher risk.

Rationale. The inactivated vaccine is safe in pregnancy and in HIV, and reduces severe disease and complications in exactly these higher-risk groups, where influenza adds to an already heavy respiratory and HIV/TB burden.

Critique. Influenza vaccine sits outside the routine EPI, so delivery and coverage are limited; the egg-based vaccine can mismatch the circulating strain; and annual reformulation and re-vaccination are needed. In a resource-constrained system a targeted risk-group strategy, rather than universal vaccination, is the appropriate use of limited doses, though cell-based and mRNA vaccines may improve the match in future.

Growing the virus in eggs can select haemagglutinin mutations that subtly change the antigen, so the vaccine matches the circulating strain less well and protects less effectively. Cell-based and recombinant production avoid this.

Egg adaptation does not make the vaccine live or transmissible, does not raise neuraminidase content, and is separate from the egg-protein allergy issue.

A haemagglutination-inhibition (HAI) titre of about 1:40 is accepted as a surrogate endpoint, so an influenza vaccine can be licensed on the antibody titre rather than a full disease trial.

Secretory IgA matters for mucosal protection but is not the licensing standard; CD8 responses have no licensed correlate; and neuraminidase and complement-fixation titres are not the accepted surrogate.

The Global Influenza Surveillance and Response System (GISRS) monitors circulating influenza worldwide and recommends each season’s vaccine strains, twice a year, once per hemisphere.

The other bodies handle polio, vaccine safety, routine immunisation delivery and acute flaccid paralysis surveillance respectively.

Inactivated influenza vaccine is recommended in every pregnancy, protecting the mother and, through transferred antibody, the newborn.

The live vaccines (intranasal influenza, MMR, varicella and yellow fever) are all contraindicated in pregnancy.