A little history…
In the introduction to this webinar, Dr. Anne Simon (infectious disease specialist, now retired) gave a quick historical update on the beginnings of vaccination. The vice-president of Actions Treatments began by recalling the definition of vaccination: that is to say, protecting an individual once morest a disease by activating their own immune system. Empirical methods of variolation appeared very early in human history, thanks to the observation that a person who survives the disease is spared in subsequent epidemics. The idea of preventing evil with evil is embodied in popular practices on the Asian and African continents.
Anne Simon gives some key dates in the history of vaccination:
– 1796: Edward Jenner makes the first scientific experiments of “vaccination” once morest smallpox.
– 1885: The principle of vaccination was explained by Louis Pasteur and his collaborators Roux and Duclaux, following the work of Robert Koch linking microbes and diseases. This discovery allowed him to develop germ mitigation techniques. The first human vaccination was that of a child once morest rabies on July 6, 1885.
– 1944: Creation of the first flu vaccine.
– 1986: Creation of the first vaccine once morest hepatitis B.
– 2020: Creation of the mRNA vaccine once morest Covid-19.
There are two main families of vaccines:
– Vaccines derived from infectious agents with live attenuated vaccines (the person is injected with a modified version of the pathogen once morest which we want them to be protected) and inactivated vaccines (which contain the infectious agent that is dead, or fragmented A vaccination method that is less effective in the long term and which requires booster shots).
– Vaccines without infectious agents. Among these, RNA (messenger RNA) vaccines of recent use (even if the principle has been known for more than ten years) are proving to be very promising and very adaptable in the face of virus mutations.
Which vaccines are recommended for PLHIV?
Pre Elisabeth Bouvet, infectiologist at Bichat – Claude Bernard Hospital (Paris) and president of the Technical Committee for Vaccinations at the Haute Autorité de Santé (HAS) presented the new vaccination recommendations for people living with HIV (PLHIV) as they will be specified in the next Expert Report which will be released in the coming months.
General principles: the ability to produce an immune response, known as immunogenicity, is generally reduced in PLHIV, particularly when the viral load is not controlled and CD4 counts are low (especially below 350/ mm3). If the viral load is undetectable and the CD4 above 500/mm3, the immune response is good, but slightly reduced and seems to be of shorter duration compared to the general population (people not infected with HIV). In addition, many studies have shown that PLHIV who had a high viral load and low CD4 (below 350/mm3) were more likely to develop serious forms of illnesses such as influenza, Covid-19, HPV (human papillomavirus), shingles, pneumococcus, meningococcus or Mpox. Point of vigilance, it is preferable to vaccinate PLHIV when the CD4 count is greater than 200/mm3). Thus, during her presentation, Prof. Bouvet unrolled the list of vaccines recommended for PLHIV:
- Seasonal flu: reminder to do every year for all PLHIV. Effective and well tolerated vaccines. High-dose vaccine recommended for PLHIV aged over 60 (strains A or B).
- Hepatitis A: same recommendations as the general population (two doses of vaccine), but check the immune response in PLHIV one to two months later and, if there is no response, give a third booster dose.
- Hepatitis B: 7% of PLHIV in France are co-infected with HBV and there is a risk of developing a chronic form. A once-in-a-lifetime vaccine for all PLHIV who have not been in contact with HBV. Three doses for the general population. A fourth dose is recommended for PLHIV for better protection. If there is a good vaccine response, monitoring (search for antibodies) every two to four years is recommended.
- Pneumococcus: well tolerated vaccine, but need to have a combined vaccine in two doses (Prenevar + two months later Pneumovax) to broaden the spectrum of vaccination coverage. This vaccine is recommended for all PLHIV regardless of CD4 count and viral load. A new pneumococcal vaccine will arrive “very soon” announces the infectious disease specialist. It will therefore be necessary to redefine this vaccination schedule.
- Human papillomavirus (HPV): increased risk in the event of HPV-induced cancer, particularly in MSM (men who have sex with men) whose CD4 counts are low. New: it is recommended to vaccinate all PLHIV from 11 to 26 years old. Nine-valent vaccine (Gardasil) at three doses (M0, M2, M6). The HAS was seized on the question of extending the age of vaccination and there will be answers during 2023, affirms the professor, but that is not on the agenda. Clinical data on the efficacy of the vaccine beyond this age are pending, specifies Prof. Bouvet.
- Covid-19: studies have shown that uncontrolled PLHIV have an increased risk of a serious form. It is therefore recommended to do the reminders and it is very likely that an annual reminder is recommended a bit like the seasonal flu.
- Mpox: recommended especially for MSM. Three doses instead of two if CD4 less than 200/mm3. Important because recent data presented at the Croi showed an increased risk of mortality in Mpox co-infected PLHIV who had less than 200 CD4 and who had not had this vaccine.
- Meningococcus: recent data indicate an increase in this infection in the population since the end of the Covid epidemic. The incidence among PLHIV is higher than that of the general population regardless of age, with an increased risk of hospitalization. In 2016, an American study found an increase in meningococcal infection among PLHIV. Quadruple vaccine. No data yet on the immunogenicity of this vaccine in PLHIV. Proposal under discussion at HAS: offer meningococcal vaccination ACYW (booster at five years) and B (booster between three and five years) to all PLHIV.
- DT Polio: a booster vaccine once morest diphtheria, tetanus and poliomyelitis is recommended every ten years in PLHIV.
Who can vaccinate?
The health crisis linked to Covid-19 has shown that it is possible to simplify access to vaccination in the event of an emergency and an ongoing law provides for an extension of vaccination to more health professionals. So concretely, who can vaccinate in France in 2023? This is the question that Dr Nicolas Terrail, hospital pharmacist at Montpellier University Hospital, answered:
- Doctors can prescribe and administer all vaccines.
- Nurses can, since April 24, 2022, administer fifteen vaccines to people over the age of 16 without prior medical prescription. Midwives can also prescribe and administer these same vaccines to pregnant women, newborn babies and those around them. List of these vaccines: seasonal flu; diphtheria; tetanus; poliomyelitis; whooping cough; human papillomaviruses; invasive pneumococcal infections; hepatitis A and B; meningococci (A, B, C, Y and W); rage. In addition, midwives are authorized to prescribe and perform vaccinations once morest rubella, measles and mumps in pregnant women or people living regularly in their environment, in newborns, vaccinations with BCG, once morest hepatitis B in combination with specific anti-HBs immunoglobulins in the newborn of a mother carrying the HBs antigen and once morest hepatitis B: newborns in Mayotte and Guyana, according to the vaccination schedule in force .
- Pharmacists can administer all vaccines with medical prescription to people over 16 years of age and can administer, without medical prescription, the vaccine once morest seasonal flu, those once morest Covid-19 and that once morest Mpox (voluntary pharmacies).
The nurse or midwife enters in the health record or the vaccination record and the shared medical file of the vaccinated person on My Health Space the name of the vaccine administered, the date of the injection and its batch number. Failing this, this healthcare professional shall issue the vaccinated person with a vaccination certificate which includes this information. If the vaccinated person does not have a shared medical file, and with their consent, the caregiver transmits this information, by secure messaging, to the vaccinated person’s attending physician.
When is an HIV vaccine?
This is the million dollar question that Professor Jean-Daniel Lelièvre, immunologist at the CHU Henri Mondor (Créteil) tried to answer in an interesting but very (too?) technical presentation. The French expert in HIV vaccination has several hats since he is also responsible for the clinical department within the Vaccine Research Institute (VRI) in France and also in charge of the Global Vaccine Enterprise for the IAS. In his presentation, Professor Lelièvre recalls the fundamentals of HIV infection. What controls an infection are the antibodies, in particular the neutralizing antibodies which will block the infection of the cells. This is the induction of a CD8 lymphocyte response. Researchers are trying to induce this type of response with a vaccine. The professor looks back on the long history of vaccine research in the prevention of HIV and its many failures. In forty years of research, nine late-stage clinical trials of HIV vaccines have been conducted, including the recent Mosaico and Imbokodo. Only one of these vaccines demonstrated any efficacy — and only at a modest level, which is not considered strong enough for regulatory approval — in the RV 144 trial, conducted in Thailand between 2003 and 2006, the results of which were published in 2009. In this trial, the level of protection was 60% at one year, but fell to 31% following three and a half years. One of the problems of HIV is the diversity of the virus with a lot of strains and this poses a major problem in the development of a vaccine once morest HIV to be active once morest all strains. The other track is that of broad-spectrum neutralizing antibodies (bNAb) which requires very specific vaccines, which are slightly different at each administration. A complex strategy, but which is starting to give interesting leads.
So what are the current avenues in HIV vaccine research? Professor Lelièvre cites the ongoing discussions: pursuing the strategy of broad-spectrum neutralizing antibodies using high-performance vaccine platforms (messenger RNA, VLP) and new adjuvants; develop mucosal vaccines, combine strategies (bNAb + T vaccine) or even study vaccination in children in whom the immune system is probably more conducive to inducing an effective response. And the professor concludes on an optimistic note by recalling that vaccine research once morest HIV has advanced fundamental clinical knowledge (methods of carrying out trials), societal (strong involvement of the patient community) which have had benefits clear indirect effects in the development of other vaccines (Covid, Ebola, etc.). There is therefore a long way to go before finding THE effective vaccine once morest HIV and making it accessible on an equitable basis on a global scale. In the meantime, effective and available tools such as Prep and Tasp have every interest in being better deployed to control the HIV epidemic in the world.